Biomedical subjects

S N Yang

Publications and source records attributed to S N Yang.

At least 37 records · Page 2Linked to original sources

PubMed2000

The prediction of late rectal complications following the treatment of uterine cervical cancer by high-dose-rate brachytherapy.

PURPOSE: This study aimed to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients with uterine cervical cancer treated with external beam radiation therapy (EBRT) and high dose rate intracavitary brachytherapy (HDRICB). METHODS AND MATERIALS: From September 1992 to December 1995, a total of 128 patients with uterine cervical cancer, who were treated and survived more than 12 months, were evaluated. After EBRT with 40-44 Gy/20-22 Fr/4-5 weeks to the whole pelvis, the dose was boosted up to 54-58 Gy with central shielding for patients with bilateral parametria of Stage IIb or greater. HDRICB consisted of three to four insertions at doses of 5-7.2 Gy (to Point A) at intervals of 1 week. Patient and treatment factors were analyzed using logistic regression analysis and the cumulative rectal biologic equivalent dose (CRBED) was calculated. RESULTS: After 30-75 months of follow-up (median, 43 months), 38 patients (29.7%) had late rectal sequelae. Patients who had Stage IIb-IVa disease, cumulative rectal dose (external RT + total ICRU rectal dose) greeater than 65 Gy, or age greater than 70 years had a high risk of developing late rectal sequelae. When 110 Gy was used as the cut-off value, 19.6% (10 of 51) of patients whose CRBED was less than 110 Gy had rectal complications, while 36.4% (28/77) of patients whose CRBED was greater than 110 Gy developed rectal complications. CONCLUSION: Risk factors of late rectal complications were advanced stage, age greater than 70 years, and cumulative rectal dose of greater than 65 Gy.

Adult↗

PubMed2000

Sustained enhancement of AMPA receptor- and NMDA receptor-mediated currents induced by dopamine D1/D5 receptor activation in the hippocampus: an essential role of postsynaptic Ca2+.

The dopaminergic system in the limbic system, particularly the D1/D5 receptor (D1/D5r), is important for certain forms of learning and memory, such as reinforcement learning, as well as the acute development of behavioral sensitization to psychostimulants such as cocaine and methamphetamine. Here, whole-cell patch-clamp recordings of evoked excitatory postsynaptic currents (EPSCs) mediated by ionotropic glutamate receptors were made from pyramidal neurons in the CA1 area of rat hippocampal slices. Activation of the D1/D5r by a selective D1/D5r agonist (+/-)-6-chloro-PB hydrobromide (SKF 81297; 3-100 microM) concentration-dependently induced a delayed-onset, sustained enhancement of EPSCs. The D1/D5r-induced effect was blocked by a selective D1/D5r antagonist (+)SCH 23390 hydrochloride (5 microM). Furthermore, the D1/D5r-induced effect involved a sustained enhancement of both the pharmacologically isolated alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate receptor-(AMPAr-) and N-methyl-D-asparate receptor- (NMDAr-) mediated EPSCs, respectively. Such persistently enhanced AMPAr- and NMDAr-mediated EPSCs were also associated with significant increases in the normalized amplitudes of the decay times of the isolated EPSCs. Blockade of NMDAr activation failed to prevent the induction of D1/D5r-induced sustained enhancement, suggesting the independence of the D1/D5r-induced effect on NMDAr activation. A rise of postsynaptic calcium was required for the induction of D1/D5r-induced sustained enhancement, being abolished by loading cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N '-tetracetic acid (BAPTA; 10 mM). Studies indicated that the D1/D5r activation induced a sustained enhancement of both the AMPAr-and NMDAr-mediated EPSCs in the hippocampus. Moreover, a rise in postsynaptic Ca2+ was necessary for triggering the D1/D5r-induced effect in the hippocampus, although the NMDAr-dependent mechanisms, such as the calcium entry via the NMDA channels, were not.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2000

Prenatal exposure to morphine alters kinetic properties of NMDA receptor-mediated synaptic currents in the hippocampus of rat offspring.

Whole-cell patch-clamp recordings of pharmacologically isolated N-methyl-D-asparate (NMDA) receptor-mediated evoked excitatory postsynaptic currents (EPSCs) were made, to study whether prenatal exposure to morphine affected functional properties of synaptic NMDA receptors in hippocampal slices of 2-week-old rat offspring from morphine-addicted mothers. The saturated amplitude of synaptic NMDA receptor-mediated EPSCs from morphine-treated offspring was about twofold larger than that from vehicle-control offspring. The apparent dissociation constant (Kd) values of NMDA receptors for Mg2+ at 0 mV were 7.5 +/- 1.4 and 7.9 +/- 1.3 mM in slices from vehicle-control and morphine-treated offspring, respectively. In addition, no distinguishable changes in the voltage-dependent nature and the reversal potential of NMDA receptors occurred in morphine-treated offspring, suggesting no alterations of Mg2+ blockade and ion selectivity to NMDA receptors. The 10-90% rise times of NMDA receptor-mediated EPSCs in morphine-treated offspring became longer than those in vehicle-control offspring. The decay of NMDA receptor-mediated EPSCs in both morphine-treated and vehicle-control offspring could be described by the sum of a fast and a slow exponential function. The slow, but not fast, decay times of synaptic NMDA receptor-mediated currents in morphine-treated offspring became slower than those in vehicle-control offspring. Collectively, these results suggest that prenatal exposure to morphine altered kinetic properties of synaptic NMDA receptors in hippocampal CA1 pyramidal neurons of rat offspring during early life. The extended duration of synaptic NMDA receptor-mediated currents presumably provided more Ca2+ entry through NMDA receptors in morphine-treated offspring, and its further prolongation by depolarization in such young offspring strengthened NMDA receptor-dependent functions. Thus, in light of pathophysiological implications within the central nervous system of morphine-treated offspring during early life, the present study may provide important insights and serve as a basis for therapeutic intervention in conditions under which NMDA receptors become abnormal.

Age Factors↗

PubMed2000

Ceramide-induced sustained depression of synaptic currents mediated by ionotropic glutamate receptors in the hippocampus: an essential role of postsynaptic protein phosphatases.

Ceramide, a sphingomyelin-derived second messenger, mediates cellular signals of cytokines such as tumor necrosis factor-alpha that are rapidly produced in the brain in response to vigorous neuronal activity and tissue injury. Using whole-cell patch-clamp recordings, the present study examined whether ceramide modulated excitatory postsynaptic currents mediated by ionotropic glutamate receptors in CA1 pyramidal neurons of rat hippocampal slices. Application of N-acetyl-D-sphingosine, a synthetic cell-permeable ceramide analog, promptly produced a slight increase of excitatory postsynaptic current amplitude lasting for about 3 min. However, this transient enhancement was followed by a profoundly delayed-onset, sustained depression of synaptic excitatory postsynaptic currents in a concentration-dependent fashion (1-30 microM). This ceramide-induced sustained depression was not associated with changes in paired-pulse facilitation, a phenomenon resulting from an alteration of presynaptic transmitter release. Dihydro-N-acetyl-D-erythro-sphingosine (10 microM), an inactive analog of N-acetyl-D-sphingosine, did not affect synaptic excitatory postsynaptic currents, indicating the specificity of N-acetyl-D-sphingosine's action. The induction of ceramide-induced sustained depression was primarily dependent on the activation of postsynaptic protein phosphatases, being considerably blocked by loading 30 nM okadaic acid (a potent inhibitor of protein phosphatases 1 and 2A) into neurons. In addition, following a stable establishment of ceramide-induced sustained depression, a protocol for inducing long-term depression caused no additional decreases in excitatory postsynaptic current amplitude, and vice versa. The study suggests that ceramide induces a long-term depressed modulation on synaptic transmission mediated by ionotropic glutamate receptors in the hippocampus, possibly through the activation of postsynaptic protein phosphatases 1 and 2A. In addition, ceramide-induced sustained depression seems to share some common mechanisms with long-term depression, such as the cascades of events resulting from the activation of protein phosphatases. Collectively, the long-term depressed modulation of ceramide on ionotropic glutamate receptor-mediated functions may be particularly important in various physiological and/or pathological conditions, in which the ceramide signaling pathway is activated in the mammalian brain.

Animals↗

PubMed2000

Abnormal activation of K(+) channels in aortic smooth muscle of rats with endotoxic shock: electrophysiological and functional evidence.

1. This study examined the role of K(+) channels in vascular hyporeactivity of rats with endotoxic shock ex vivo. 2. At the end of the in vivo experiments, thoracic aortas were removed from endotoxaemic and control rats. After removal of the endothelium, aortic segments were mounted in myographs for recording of isometric tension and smooth muscle membrane potential. 3. Membrane potentials recorded from endotoxaemic rats were hyperpolarized compared to those of the controls. This hyperpolarization was partially reversed by tetraethylammonium, charybdotoxin or glibenclamide, but not significantly affected by apamin. The hyperpolarization was also partially attenuated by N(omega)-nitro-L-arginine methyl ester (L-NAME) or 1H:-[1,2,4]oxadiazolo[4,3-a]quinoxalin-l-one (ODQ). 4. In phenylephrine-contracted aortic rings, both agonists of K(+) channels, NS1619 and pinacidil, induced greater relaxations and re-polarizations in the preparations obtained from endotoxaemic rats. The NS1619-induced relaxation and re-polarization in arteries from endotoxaemic rats were partially inhibited by tetraethylammonium and completely inhibited by charybdotoxin, L-NAME or ODQ, but not significantly affected by apamin. Similarly, the greater relaxation and re-polarization induced by pinacidil in arteries from endotoxaemic rats were also inhibited by glibenclamide, L-NAME or ODQ. However, these inhibitors had no significant effect on relaxations and re-polarizations induced by NS1619 and pinacidil in arteries from controls. 5. This study provides the electrophysiological and functional evidence showing an abnormal activation of K(+) channels in vascular smooth muscle in animals with endotoxic shock. Our observations suggest that overproduction of nitric oxide causes an activation of large conductance Ca(2+)-activated K(+) channels and ATP-sensitive K(+) channels which contributes to endotoxin-mediated vascular hyporeactivity.

Animals↗

PubMed2000

Synaptotagmin III isoform is compartmentalized in pancreatic beta-cells and has a functional role in exocytosis.

Synaptotagmin is involved in Ca2+-regulated secretion and has been suggested to serve as a general Ca2+ sensor on the membrane of secretory vesicles in neuronal cells. Insulin exocytosis from the pancreatic beta-cell is an example of a Ca2+-dependent secretory process. Previous studies of pancreatic beta-cells were unable to show presence of synaptotagmin I. We now present biochemical and immunohistochemical data showing that synaptotagmin III is present in pancreatic beta-cells as well as in the insulin-secreting cell line HIT-T15 and in rat insulinoma. By subcellular fractionation, we found synaptotagmin III in high-density fractions together with insulin and secretogranin I, indicating colocalization of synaptotagmin III and insulin in secretory granules. We could also show that blockade of synaptotagmin III by a specific antibody inhibited Ca2+-induced changes in beta-cell membrane capacitance, suggesting that synaptotagmin III is part of the functional protein complex regulating beta-cell exocytosis. The synaptotagmin III antibody did not affect the activity of the voltage-gated L-type Ca2+-channel. These findings are compatible with the view that synaptotagmin III, because of its distinct localization in the pancreatic beta-cell, functionally modulates insulin exocytosis. This indicates that synaptotagmin may have a general role in the regulation of exocytosis not only in neuronal cells but also in endocrine cells.

Animals↗

PubMed2000

Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide.

A massive degeneration of dopamine-containing neurons in the substantia nigra (SN) in the midbrain is characteristic of Parkinson's disease. Inflammation in the brain has long been speculated to play a role in the pathogenesis of this neurological disorder. Recently, we reported that treatment of primary rat mesencephalic mixed neuron-glia cultures with lipopolysaccharide (LPS) led to the activation of microglia, resident immune cells of the brain, and subsequent death of dopaminergic neurons. The LPS-induced degeneration of dopaminergic neurons was significantly attenuated by the opiate receptor antagonist (-)-naloxone and its inactive isomer (+)-naloxone, with equal potency, through an inhibition of microglial activation and their production of neurotoxic factors. In this study, injection of LPS into the rat SN led to the activation of microglia and degeneration of dopaminergic neurons: microglial activation was observed as early as 6 h and loss of dopaminergic neurons was detected 3 days after the LPS injection. Furthermore, the LPS-induced loss of dopaminergic neurons in the SN was time- and LPS concentration-dependent. Systemic infusion of either (-)-naloxone or (+)-naloxone inhibited the LPS-induced activation of microglia and significantly reduced the LPS-induced loss of dopaminergic neurons in the SN. These in vivo results combined with our cell culture observations confirmed that naloxone protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation and suggest that naloxone would have therapeutic efficacy in the treatment of inflammation-related neurological disorders. In addition, the inflammation-mediated degeneration of dopaminergic neurons in the rat SN resulting from the targeted injection of LPS may serve as a useful model to gain further insights into the pathogenesis of Parkinson's disease.

Animals↗

PubMed1999

Syntaxin 1 interacts with the L(D) subtype of voltage-gated Ca(2+) channels in pancreatic beta cells.

Interaction of syntaxin 1 with the alpha(1D) subunit of the voltage-gated L type Ca(2+) channel was investigated in the pancreatic beta cell. Coexpression of the enhanced green fluorescent protein-linked alpha(1D) subunit with the enhanced blue fluorescent protein-linked syntaxin 1 and Western blot analysis together with subcellular fractionation demonstrated that the alpha(1D) subunit and syntaxin 1 were colocalized in the plasma membrane. Furthermore, the alpha(1D) subunit was coimmunoprecipitated efficiently by a polyclonal antibody against syntaxin 1. Syntaxin 1 also played a central role in the modulation of L type Ca(2+) channel activity because there was a faster Ca(2+) current run-down in cells incubated with antisyntaxin 1 compared with controls. In parallel, antisyntaxin 1 markedly reduced insulin release in both intact and permeabilized cells, subsequent to depolarization with K(+) or exposure to high Ca(2+). Exchanging Ca(2+) for Ba(2+) abolished the effect of antisyntaxin 1 on both Ca(2+) channel activity and insulin exocytosis. Moreover, antisyntaxin 1 had no significant effects on Ca(2+)-independent insulin release trigged by hypertonic stimulation. This suggests that there is a structure-function relationship between the alpha(1D) subunit of the L type Ca(2+) channel and the exocytotic machinery in the pancreatic beta cell.

Animals↗

PubMed1999

Presynaptic involvement of nitric oxide in dopamine D1/D5 receptor-induced sustained enhancement of synaptic currents mediated by ionotropic glutamate receptors in the rat hippocampus.

Using whole-cell patch-clamp recordings, the study tested the possibility whether nitric oxide (NO) was involved in dopamine D1/D5 receptor (D1/D5r)-induced sustained enhancement of excitatory postsynaptic currents (EPSCs) mediated by ionotropic glutamate receptors in rat hippocampal slices. Activation of D1/D5r by a selective agonist, 50 microM (+/-)-6-chloro-PB hydrobromide, elicited not only a sustained enhancement but also an increased frequency of spontaneous EPSC. The D1/D5r-induced effect was associated with decreases in paired-pulse facilitation (PPF). A selective inhibitor of neuronal NO synthase (nNOS), 100 microM 7-nitroindazole monosodium salt, substantially attenuated both the magnitudes of D1/D5r-induced enhancement and PPF decrease. These results suggest that presynaptic effects mediated by NO, possibly synthesized by nNOS, are involved in D1/D5-induced sustained enhancement of synaptic currents mediated by ionotropic glutamate receptors in the hippocampus.

Animals↗

PubMed1999

Activation of gonadotropin-releasing hormone receptors produces neuronal excitation in the rat hippocampus.

Whole-cell patch-clamp recordings of evoked action potentials were made in CA1 and CA3 pyramidal neurons of rat hippocampal slices. Previously we have demonstrated that activation of gonadotropin-releasing hormone (GnRH) receptors induces a long-lasting enhancement of synaptic transmission mediated by ionotropic glutamate receptors in CA1 pyramidal neurons of rat hippocampal slices. Here, we further studied whether activation of GnRH receptors could modulate intrinsic neuronal excitability in CA1 and CA3 pyramidal neurons of rat hippocampal slices. The use of a specific GnRH analog, leuprolide (10(-8) M), elicited a relatively long-term increase in evoked action potentials in CA1 and CA3 pyramidal neurons, respectively. The GnRH receptor-induced increase in evoked action potentials in both CA1 and CA3 pyramidal neurons could be abolished by a potent GnRH receptor antagonist, [acetyl-3,4-dehydro-Pro1,D-p-F-Phe2,D-Trp(3,6)]-LHRH (10(-8) M). The present study suggests that activation of GnRH receptors can lead to an increase of intrinsic neuronal excitability of both CA1 and CA3 pyramidal neurons in the rat hippocampus, an important integrative region for reproductive process, both endocrinologically and behaviorally.

Action Potentials↗

PubMed1999

Activation of gonadotropin-releasing hormone receptors induces a long-term enhancement of excitatory postsynaptic currents mediated by ionotropic glutamate receptors in the rat hippocampus.

Whole-cell patch-clamp recordings were made from CA1 pyramidal neurons of the rat hippocampus to study the modulation of gonadotropin-releasing hormone (GnRH) on synaptic transmission mediated by ionotropic glutamate receptors. Leuprolide (10(-9)-10(-7) M), a specific GnRH analog, concentration-dependently elicited a long-lasting potentiation of excitatory postsynaptic currents (EPSCs) mediated by ionotropic glutamate receptors. GnRH receptor-induced synaptic potentiation was blocked by 1 microM [Acetyl-3,4-dehydro-Pro1,D-p-F-Phe2,D-Trp3,6]-LHRH, a specific GnRH receptor antagonist. Furthermore, GnRH receptor-induced synaptic potentiation was associated with the stimulation of protein kinase C (PKC), being considerably attenuated by a potent PKC inhibitor (30 microM H-7). The results suggest a long-term enhanced modulation of GnRH on synaptic transmission mediated by ionotropic glutamate receptors, possibly via the actions of PKC in the hippocampus that is an important integrative system in the regulation of reproductive processes.

Animals↗

PubMed1999

Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation.

Long-term potentiation (LTP) and long-term depression (LTD), two prominent forms of synaptic plasticity at glutamatergic afferents to CA1 hippocampal pyramidal cells, are both triggered by the elevation of postsynaptic intracellular calcium concentration ([Ca2+]i). To understand how one signaling molecule can be responsible for triggering two opposing forms of synaptic modulation, different postsynaptic [Ca2+]i elevation patterns were generated by a new caged calcium compound nitrophenyl-ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid in CA1 pyramidal cells. We found that specific patterns of [Ca2+]i elevation selectively activate LTP or LTD. In particular, only LTP was triggered by a brief increase of [Ca2+]i with relatively high magnitude, which mimics the [Ca2+]i rise during electrical stimulation typically used to induce LTP. In contrast, a prolonged modest rise of [Ca2+]i reliably induced LTD. An important implication of the results is that both the amplitude and the duration of an intracellular chemical signal can carry significant biological information.

Animals↗

PubMed1998

Free radicals are involved in methylmethacrylate-induced neurotoxicity in human primary neocortical cell cultures.

Methylmethacrylate monomer (MMA), a highly volatile material, has been extensively used for the construction of complete or partial dental prostheses. While previous studies have indicated a variety of complications and untoward side-effects associated with its use, the possible neurotoxicity induced by this monomer has not been addressed. In this study, we have investigated the MMA-produced neuronal injury in human neuron-enriched primary culture. Embryonic brain tissue (8-10 weeks postconception) was used for the primary neuron-enriched culture. Phase-contrast microscopy was used to evaluate morphological changes of cultured neurons. Extracellular concentrations of lactate dehydrogenase (LDH) and nitrite was measured from the culture medium to assess the magnitude of neuronal damage and nitric oxide formation, respectively. Neocortical neurons exposed to the monomer (1/200, Vmonomer/Vglycerol) for two days resulted in a significant increase in the LDH level but monomer (1/20000, 1/2000, or 1/200; Vmonomer/Vglycerol) failed to increase the nitrite level. Morphologically, the neurons subjected to monomer treatment exhibited irregular shrunken cell bodies with dystrophic and/or fragmented neurities, or even cell lysis. Moreover, superoxide dismutase plus catalase or vitamin C pretreatment protected against monomer-induced neurotoxicity. Our results suggest that this neurotoxicity can not likely be attributed to the cytotoxic effects of nitric oxide but may be mediated through the toxicity of superoxide and other free radicals. This is the first time, to our knowledge, that neurotoxicity induced by MMA has been demonstrated in human cortical neurons.

Ascorbic Acid↗

PubMed1998

The involvement of nitric oxide in synergistic neuronal damage induced by beta-amyloid peptide and glutamate in primary rat cortical neurons.

Abnormal extracellular accumulation of beta-amyloid (Abeta), the major component of senile plaques in the Alzheimer's brain and the excitatory amino acid glutamate are both considered to be associated with neurodegeneration. We studied whether nitric oxide (NO) was involved in neuronal damage induced by Abeta and glutamate in primary rat cortical neurons. Our results demonstrated that (1) Both neuronal damage and NO production were synergistically induced by Abeta-(25-35) and glutamate; (2) This synergistic neuronal damage induced by Abeta-(25-35) and glutamate was attenuated by selective inhibitors of NO synthase. We propose that cytotoxic characteristics of NO, at least in part, are involved in the synergistic neuronal damage induced by Abeta and glutamate, presumably seen in Alzheimer's brains.

Alzheimer Disease↗

PubMed1998

Cysteine string protein (CSP) is an insulin secretory granule-associated protein regulating beta-cell exocytosis.

Cysteine string proteins (CSPs) are novel synaptic vesicle-associated protein components characterized by an N-terminal J-domain and a central palmitoylated string of cysteine residues. The cellular localization and functional role of CSP was studied in pancreatic endocrine cells. In situ hybridization and RT-PCR analysis demonstrated CSP mRNA expression in insulin-producing cells. CSP1 mRNA was present in pancreatic islets; both CSP1 and CSP2 mRNAs were seen in insulin-secreting cell lines. Punctate CSP-like immunoreactivity (CSP-LI) was demonstrated in most islets of Langerhans cells, acinar cells and nerve fibers of the rat pancreas. Ultrastructural analysis showed CSP-LI in close association with membranes of secretory granules of cells in the endo- and exocrine pancreas. Subcellular fractionation of insulinoma cells showed CSP1 (34/36 kDa) in granular fractions; the membrane and cytosol fractions contained predominantly CSP2 (27 kDa). The fractions also contained proteins of 72 and 70 kDa, presumably CSP dimers. CSP1 overexpression in INS-1 cells or intracellular administration of CSP antibodies into mouse ob/ob beta-cells did not affect voltage-dependent Ca2+-channel activity. Amperometric measurements showed a significant decrease in insulin exocytosis in individual INS-1 cells after CSP1 overexpression. We conclude that CSP is associated with insulin secretory granules and that CSP participates in the molecular regulation of insulin exocytosis by mechanisms not involving changes in the activity of voltage-gated Ca2+-channels.

Animals↗

PubMed1998

Metabotropic glutamate receptors are involved in calcium-induced LTP of AMPA and NMDA receptor-mediated responses in the rat hippocampus.

Effects of metabotropic glutamate (mGlu) receptors on calcium-induced long-term potentiation (LTP) of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components were investigated in rat hippocampal slices using whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs). Calcium-induced LTP comprises a parallel, long-lasting increase of AMPA and NMDA receptor-mediated components. The calcium-induced LTP of the AMPA receptor-mediated component can be significantly attenuated by the use of a selective NMDA antagonist. (R.S)-alpha-methyl-4-carboxyphenylglycine (MCPG), a selective antagonist of mGlu receptors, abolished the long-lasting increase of both AMPA and NMDA receptor-mediated components observed in calcium-induced LTP. In current clamp mode, the application of a high calcium alone or Schaffer fiber stimulation alone (20 Hz) only generated a short-term increase in the firing rate of evoked action potentials. Conversely, a long-term increase in the firing rate was observed if Schaffer fiber stimulation (20 Hz) accompanied the perfusion of high calcium. These results suggest that calcium-induced LTP involves a parallel, long-lasting enhancement in ionotropic AMPA and NMDA receptor-mediated components. More importantly, the mGlu receptor plays a critical role in the establishment of both AMPA and NMDA receptor-mediated components underlying calcium-induced LTP. In addition, the present study also described an experimental condition in which the coapplication of the high calcium pulse and Schaffer fiber stimulation (20 Hz) can synergistically elicit a long-term increase of neuronal excitability.

Action Potentials↗

PubMed1997

Increased potency of neuropeptide Y to antagonize alpha2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat.

The regulation by neuropeptide Y of alpha2-adrenoceptors in the nucleus tractus solitarii was evaluated in the adult normotensive Wistar Kyoto rat and the adult spontaneously hypertensive rat. The microinjection of a submaximal dose of l-noradrenaline (800 pmol in 50 nl) alone into the nucleus tractus solitarii produced a significant reduction in the mean arterial blood pressure in either strain. The threshold dose (1 pmol in 50 nl) of neuropeptide Y(1-36) for the vasodepressor response in the Wistar Kyoto rat was five times higher than that (0.2 pmol in 50 nl) in the spontaneously hypertensive rat. Furthermore, neuropeptide Y(1-36) at 0.2 pmol in 50 nl could significantly counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl) in the spontaneously hypertensive rat, but not in the Wistar Kyoto rat, in which 1 pmol in 50 nl of neuropeptide Y(1-36) must be employed to counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl), although the vasodepressor responses are of a similar magnitude. The in situ hybridization and quantitative receptor autoradiographical experiments showed that the alpha2A-adrenoceptor messenger RNA levels and the B(max) value of the alpha2-adrenoceptor agonist [3H]p-aminoclonidine binding sites measured in the nucleus tractus solitarii of the spontaneously hypertensive rat were substantially lower than those in the Wistar Kyoto rat. The quantitative receptor autoradiographical results were consistent with the cardiovascular results and showed that in the spontaneously hypertensive rat, neuropeptide Y(1-36) at 1 nM led to a significant increase in the K(d) value of [3H]p-aminoclonidine binding sites. In the Wistar Kyoto rat, neuropeptide Y(1-36) produced this effect only at 10 nM. The present study provides evidence for an increase of the potency of neuropeptide Y(1-36) to antagonistically modulate alpha2-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat. This enhanced antagonistic action may partly be related to a reduction in the number of alpha2A-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat, since a decrease has been observed in the alpha2A-adrenoceptor messenger RNA levels and the alpha2-adrenoceptor binding sites in the spontaneously hypertensive rat. This increased potency of neuropeptide Y(1-36) to antagonize alpha2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat may contribute to the development of high blood pressure in this hypertensive strain.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1997

Localization of angiotensin II AT1 receptor-like immunoreactivity in catecholaminergic neurons of the rat medulla oblongata.

There exist at least two distinct subtypes of angiotensin II receptors in the brain, namely the AT1 and AT2 subtypes. The high density of angiotensin II AT1 receptors is present in the medulla oblongata. The AT1 subtype of angiotensin II receptors mainly mediates central cardiovascular events. In the present study a polyclonal antibody against the angiotensin II AT1 receptor and a monoclonal antibody against tyrosine hydroxylase were employed to evaluate the possible presence of angiotensin II AT1 receptor-like immunoreactivity in the catecholaminergic neurons of the rat medulla oblongata by means of the double colour immunofluorescence technique. A weak, diffuse cytoplasmic angiotensin II AT1 receptor-like immunoreactivity was observed in almost all the catecholaminergic cell bodies of the A2, C1, C2 and C3 cell groups, except those of the A1 cell group containing moderately intense, diffuse cytoplasmic angiotensin II AT1 receptor-like immunoreactivity, occasionally found in the noradrenergic dendrites of the A1 cell group. There was a higher density of the angiotensin II AT1 receptor-like immunoreactive profiles in the A2 cell group area than in other catecholaminergic cell group areas. In addition, the angiotensin II AT1 receptor-like immunoreactivity was seen in non-catecholaminergic neurons. The present results provide evidence for the existence of the specific angiotensin II AT1 receptor-like immunoreactivity in the noradrenergic and adrenergic neurons of the rat medulla oblongata known to have a cardiovascular role. Thus, the findings support the view that angiotensin II AT1 receptors in the medulla oblongata participate in cardiovascular control and indicate a cellular substrate for the documented interaction between the angiotensin II and adrenergic transmission lines in cardiovascular function at the level of the nucleus tractus solitarii.

Adrenergic Fibers↗