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N Mores

Publications and source records attributed to N Mores.

At least 19 recordsLinked to original sources
PubMed2001

Regulation of Ca2+-sensitive adenylyl cyclase in gonadotropin-releasing hormone neurons.

In immortalized GnRH neurons, cAMP production is elevated by increased extracellular Ca2+ and the Ca2+ channel agonist, BK-8644, and is diminished by low extracellular Ca2+ and treatment with nifedipine, consistent with the expression of adenylyl cyclase type I (AC I). Potassium-induced depolarization of GT1-7 neurons causes a dose-dependent monotonic increase in [Ca2+]i and elicits a bell-shaped cAMP response. The inhibitory phase of the cAMP response is prevented by pertussis toxin (PTX), consistent with the activation of G(i)-related proteins during depolarization. Agonist activation of the endogenous GnRH receptor in GT1-7 neurons also elicits a bell-shaped change in cAMP production. The inhibitory action of high GnRH concentrations is prevented by PTX, indicating coupling of the GnRH receptors to G(i)-related proteins. The stimulation of cAMP production by activation of endogenous LH receptors is enhanced by low (nanomolar) concentrations of GnRH but is abolished by micromolar concentrations of GnRH, again in a PTX-sensitive manner. These findings indicate that GnRH neuronal cAMP production is maintained by Ca2+ entry through voltage-sensitive calcium channels, leading to activation of Ca2+-stimulated AC I. Furthermore, the Ca2+ influx-dependent activation of AC I acts in conjunction with AC-regulatory G proteins to determine basal and agonist-stimulated levels of cAMP production.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2000

Local regulation of gonadotroph function by pituitary gonadotropin-releasing hormone.

Cultured rat pituitary cells and immortalized pituitary gonadotrophs (alphaT3-1 cells) express specific messenger RNA transcripts for GnRH and exhibit positive immunostaining for the GnRH peptide. Each cell type released GnRH during both static culture and perifusion, albeit in lesser amounts than cultured hypothalamic cells and GT1-7 neurons. In perifused pituitary cells, exposure to a GnRH agonist stimulated the release of GnRH as well as LH. In contrast, treatment with a GnRH receptor antagonist or with GnRH antiserum decreased basal LH release. In pituitary cell cultures, a small proportion of gonadotrophs exhibited high amplitude and low frequency baseline Ca2+ oscillations in the absence of GnRH stimulation. Such spontaneous oscillations were comparable to those induced by picomolar concentrations of GnRH and could be abolished by treatment with a GnRH antagonist. These in vitro findings indicate that locally produced GnRH causes low level activation of pituitary GnRH receptors, induces spontaneous intracellular Ca2+ oscillations, and contributes to basal LH secretion in cultured pituitary cells. In vivo, such autocrine or paracrine actions of pituitary-derived GnRH could provide a mechanism for the maintenance of optimal responsiveness of the gonadotrophs to pulses of GnRH arising in the hypothalamus. The presence and actions of GnRH in the anterior pituitary gland, the major site of expression of GnRH receptors, suggest that local regulatory effects of the neuropeptide could supplement the primary hypothalamic mechanism for the control of episodic gonadotropin secretion.

Animals↗
PubMed1999

No cardiovascular effects of single-dose pseudoephedrine in patients with essential hypertension treated with beta-blockers.

OBJECTIVE: The use of the decongestant pseudoephedrine has been cautioned in patients with arterial hypertension, due to the possible rise in blood pressure induced by the sympathostimulatory properties of the drug. This effect could be enhanced in hypertensives treated with beta-blockers, in whom the vasoconstrictor effect of alpha-adrenergic stimulation is unbalanced. The purpose of this study was to investigate the cardiovascular response to pseudoephedrine in hypertensive patients treated with different types of beta-blockers. METHODS: We recruited 29 (18 males) mild-to-moderate essential hypertensive patients [mean age 49(2) years] in a randomized, placebo-controlled, crossover trial. All participants received either placebo, or a nonselective (propranolol 160 mg once daily) or a selective (atenolol 100 mg once daily) beta-blocker for 1 week. At the end of each period, all patients received a single oral dose of pseudoephedrine (60 mg) and their blood pressure and heart rate were monitored at repeated intervals for 2 h. RESULTS: After 1 week of propranolol or atenolol, patients had significantly lower systolic blood pressure and heart rate than after placebo, whereas diastolic blood pressure was not significantly modified. The acute administration of pseudoephedrine did not change systolic and diastolic blood pressure and heart rate from baseline at the end of any of the treatment periods. CONCLUSIONS: A standard oral dose of pseudoephedrine does not significantly affect blood pressure values in hypertensive patients treated with beta-blockers, and therefore may be safely used in this subset of patients.

Adrenergic alpha-Agonists↗
PubMed1999

Identification of two novel Mycobacterium avium allelic variants in pig and human isolates from Brazil by PCR-restriction enzyme analysis.

Mycobacterium avium complex (MAC) is composed of environmental mycobacteria found widely in soil, water, and aerosols that can cause disease in animals and humans, especially disseminated infections in AIDS patients. MAC consists of two closely related species, M. avium and M. intracellulare, and may also include other, less-defined groups. The precise differentiation of MAC species is a fundamental step in epidemiological studies and for the evaluation of possible reservoirs for MAC infection in humans and animals. In this study, which included 111 pig and 26 clinical MAC isolates, two novel allelic M. avium PCR-restriction enzyme analysis (PRA) variants were identified, differing from the M. avium PRA prototype in the HaeIII digestion pattern. Mutations in HaeIII sites were confirmed by DNA sequencing. Identification of these isolates as M. avium was confirmed by PCR with DT1-DT6 and IS1245 primers, nucleic acid hybridization with the AccuProbe system, 16S ribosomal DNA sequencing, and biochemical tests. The characterization of M. avium PRA variants can be useful in the elucidation of factors involved in mycobacterial virulence and routes of infection and also has diagnostic significance, since they can be misidentified as M. simiae II and M. kansasii I if the PRA method is used in the clinical laboratory for identification of mycobacteria.

Alleles↗
PubMed1999

Autocrine regulation of gonadotropin-releasing hormone secretion in cultured hypothalamic neurons.

Episodic hormone secretion is a characteristic feature of the hypothalamo-pituitary-gonadal system, in which the profile of gonadotropin release from pituitary gonadotrophs reflects the pulsatile secretory activity of GnRH-producing neurons in the hypothalamus. Pulsatile release of GnRH is also evident in vitro during perifusion of immortalized GnRH neurons (GT1-7 cells) and cultured fetal hypothalamic cells, which continue to produce bioactive GnRH for up to 2 months. Such cultures, as well as hypothalamic tissue from adult rats, express GnRH receptors as evidenced by the presence of high-affinity GnRH binding sites and GnRH receptor transcripts. Furthermore, individual GnRH neurons coexpress GnRH and GnRH receptors as revealed by double immunostaining of hypothalamic cultures. In static cultures of hypothalamic neurons and GT1-7 cells, treatment with the GnRH receptor antagonist, [D-pGlu1, D-Phe2, D-Trp(3,6)]GnRH caused a prominent increase in GnRH release. In perifused hypothalamic cells and GT1-7 cells, treatment with the GnRH receptor agonist, des-Gly10-[D-Ala6]GnRH N-ethylamide, reduced the frequency and increased the amplitude of pulsatile GnRH release, as previously observed in GT1-7 cells. In contrast, exposure to the GnRH antagonist analogs abolished pulsatile secretion and caused a sustained and progressive increase in GnRH release. These findings have demonstrated that GnRH receptors are expressed in hypothalamic GnRH neurons, and that receptor activation is required for pulsatile GnRH release in vitro. The effects of GnRH agonist and antagonist analogs on neuropeptide release are consistent with the operation of an ultrashort-loop autocrine feedback mechanism that exerts both positive and negative actions that are necessary for the integrated control of GnRH secretion from the hypothalamus.

Animals↗
PubMed1998

Mediation of cyclic AMP signaling by the first intracellular loop of the gonadotropin-releasing hormone receptor.

The gonadotropin-releasing hormone (GnRH) receptor, which is a unique G protein-coupled receptor without a C-terminal cytoplasmic domain, activates both inositol phosphate (InsP) and cAMP signaling responses. The function of the highly basic first intracellular (1i) loop of the GnRH receptor in signal transduction was evaluated by mutating selected residues located in its N and C termini. Replacements of Leu58, Lys59, Gln61, and Lys62 at the N terminus, and Leu73, Ser74, and Leu80 at the C terminus, caused no change in binding affinity. The agonist-induced InsP and cAMP responses of the Q61E and K59Q,K62Q receptors were also unaffected, but the L58A receptor showed a normal InsP response and an 80% decrease in cAMP production. At the C terminus, the InsP response of the L73R receptor was normal, but cAMP production was reduced by 80%. The EC50 for GnRH-induced InsP responses of the S74E and L80A receptors was increased by about one order of magnitude, and the cAMP responses were essentially abolished. These findings indicate that cAMP signaling from the GnRH receptor is dependent on specific residues in the 1i loop that are not essential for activation of the phosphoinositide signaling pathway.

Amino Acid Sequence↗
PubMed1998

Muscarinic regulation of intracellular signaling and neurosecretion in gonadotropin-releasing hormone neurons.

Agonist activation of cholinergic receptors expressed in perifused hypothalamic and immortalized GnRH-producing (GT1-7) cells induced prominent peaks in GnRH release, each followed by a rapid decrease, a transient plateau, and a decline to below basal levels. The complex profile of GnRH release suggested that acetylcholine (ACh) acts through different cholinergic receptor subtypes to exert stimulatory and inhibitory effects on GnRH release. Whereas activation of nicotinic receptors caused a transient increase in GnRH release, activation of muscarinic receptors inhibited basal GnRH release. Nanomolar concentrations of ACh caused dose-dependent inhibition of cAMP production that was prevented by pertussis toxin (PTX), consistent with the activation of a plasma-membrane Gi protein. Micromolar concentrations of ACh also caused an increase in phosphoinositide hydrolysis that was inhibited by the M1 receptor antagonist, pirenzepine. In ACh-treated cells, immunoblot analysis revealed that membrane-associated G(alpha q/11) immunoreactivity was decreased after 5 min but was restored at later times. In contrast, immunoreactive G(alpha i3) was decreased for up to 120 min after ACh treatment. The agonist-induced changes in G protein alpha-subunits liberated during activation of muscarinic receptors were correlated with regulation of their respective transduction pathways. These results indicate that ACh modulates GnRH release from hypothalamic neurons through both M1 and M2 muscarinic receptors. These receptor subtypes are coupled to Gq and Gi proteins that respectively influence the activities of PLC and adenylyl cyclase/ion channels, with consequent effects on neurosecretion.

Acetylcholine↗
PubMed1998

Histochemical and lectinhistochemical studies on nasal mucosa of pigs with or without respiratory diseases.

Histochemical and lectinhistochemical examinations were carried out on nasal mucosa of pigs with or without respiratory diseases. As the results, both acid and neutral mucins coexisted in nasal mucosa of normal pigs while acid sialomucins were mainly observed in nasal mucosa of pigs infected with Bordetella bronchiseptica and/or Pasteurella multocida. Lectinhistochemistry revealed that the nasal epithelial cells of normal pigs were rich in N-acetylgalactosamine, fucose and N-acetyl-glucosamine residues which showed a tendency to disappear in porcine cytomegalovirus infection and to increase in atrophic rhinitis, respectively.

Animals↗
PubMed1997

Extracellular sodium removal increases release of neuropeptide Y-like immunoreactivity from rat brain hypothalamic synaptosomes: involvement of intracellular acidification.

Rat hypothalamic synaptosomes were exposed via superfusion to various stimuli and the release of neuropeptide Y-like immunoreactivity (NPY-LI) was measured by means of radioimmunoassay procedures. High KCl (15-50 mM) concentration dependently evoked NPY-LI release; the evoked overflow reached a plateau at 30 mM KCl and was abolished in the absence of Ca2+ ions. Furthermore, a remarkable NPY-LI overflow was obtained when extracellular Na+ ions were removed. Low external Na(+)-evoked NPY-LI release was independent of the presence of Ca2+ ions from the superfusion medium. It is well known that the reduction of external Na+ ions activates the release of several neurotransmitters through an inversion of the uptake-carrier working direction; but such mechanisms, involving Na(+)-dependent uptake, have never been described for neuropeptides. The alteration of the extracellular Na+ concentration is able to modify the concentration of the intracellular Ca2+ and H+ ions. In fact, the concentrations of these two ions are regulated through Na(+)-dependent exchange mechanisms across the membrane. Amiloride, blocking the Na+/H+ exchanger, was able to maintain low Na(+)-evoked NPY-LI release, underlying that the blockade of the exchanger preserves the H+ accumulation induced by the reduction of the external Na+ ions. NPY-LI release could also be stimulated by nigericine, a proton ionophore, showing that the intracellular acidification is responsible for NPY-LI release. Intracellular acidification may stimulate Ca2+ ion release from intracellular stores, as has been shown by other workers. Large dense-core vesicles containing the peptide appear to be more sensitive to local intracellular Ca2+ release compared with extracellular Ca2+ ion entry through voltage-dependent channels.

Amiloride↗
PubMed1997

Platelet alpha 2-adrenergic receptors in hypercholesterolemia: relationship between binding studies and epinephrine-induced platelet aggregation.

BACKGROUND: Platelets isolated from patients with hypercholesterolemia are more sensitive in vitro to various aggregating agents, including epinephrine, than those isolated from normocholesterolemic subjects. Increased platelet reactivity is one mechanism that may explain the enhanced risk of thromboembolism in hypercholesterolemia. This study assessed whether platelet hyperreactivity to epinephrine in hypercholesterolemia is associated with higher alpha 2-adrenergic receptor density or affinity for epinephrine. METHODS: Platelet aggregation and binding studies, with use of [3H]yohimbine as ligand, were performed on platelets isolated from 30 patients with type IIa hypercholesterolemia and 23 control subjects. RESULTS: Platelet aggregation in response to epinephrine was significantly higher in patients with hypercholesterolemia than in control subjects. A statistically significantly higher alpha 2-adrenergic receptor density was observed in a subgroup of 13 patients with hypercholesterolemia than in 13 sex- and age-matched control subjects (280 +/- 61 and 230 +/- 49 fmol/mg protein respectively; p < 0.03), but no difference was observed in receptor affinity for the ligand. In these subgroups plasma total and levels of low-density lipoprotein (LDL) cholesterol were inversely correlated with platelet aggregation but directly correlated with platelet receptor density. CONCLUSION: Platelet alpha 2-adrenergic receptor density is increased in hypercholesterolemia and directly correlates with plasma total and levels of LDL cholesterol, providing at least a partial explanation for the enhanced platelet response to epinephrine that is observed in hypercholesterolemia.

Adrenergic alpha-Antagonists↗
PubMed1996

Activation of LH receptors expressed in GnRH neurons stimulates cyclic AMP production and inhibits pulsatile neuropeptide release.

The GT1-7 cell line of immortalized GnRH neurons has been shown to express receptors for GnRH, LH, and prolactin, as well as a variety of other hormones and transmitters. Treatment of GT1-7 cells with hCG caused a dose-dependent increase in cAMP production, with a rapid increase during the first 15 min and a subsequent decrease that was prevented by pre-treatment with pertussis toxin. Furthermore, the stimulatory effect of cholera toxin on cAMP production was inhibited by hCG in a dose-dependent manner. These data indicate that the LH receptors expressed in GT1-7 cells are coupled to adenylyl cyclase both stimulatory (Gs) and inhibitory (Gi) proteins. In perifused cell cultures, treatment with forskolin and 8-bromo cAMP increased the amplitude of spontaneous GnRH release. However, treatment with nanomolar concentrations of hCG abolished pulsatile GnRH release from both GT1-7 cells and rat hypothalamic cells. The similarity of hCG action on pulsatile GnRH release to that of extracellular Ca2+ depletion and calcium channel antagonists, and its partial resistance to potassium-induced depolarization, suggest that it results from inhibition of plasma-membrane ion channel activity. It is probable that the inhibitory action of hCG on pulsatile GnRH release is responsible for initiation of the suppression of pituitary LH secretion during pregnancy.

Adenylate Cyclase Toxin↗
PubMed1995

Presynaptic A2-adrenoceptors and neuropeptide Y Y2 receptors inhibit [3H]noradrenaline release from rat hypothalamic synaptosomes via different mechanisms.

Presynaptic receptors may reduce transmitter release with different mechanisms. Both the alpha 2-agonist, clonidine and the Y2-agonist, neuropeptide Y fragment 13-36 (NPY 13-36), induce a concentration-dependent inhibition of the 4-aminopyridine (4-AP)-evoked [3H]noradrenaline ([3H]NA) release from hypothalamic synaptosomes. Changes in alpha 2- and Y2-modulation of noradrenaline (NA) release were observed by lowering the calcium influx with the use of omega-conotoxin (omega-CgTx), a calcium-channel blocking agent. In these experimental conditions, clonidine was less active, whereas NPY 13-36 preserved its efficacy. It therefore seems possible that presynaptic alpha 2-adrenoceptors can primarily inhibit NA release by reducing calcium influx via voltage-sensitive calcium channels (VSCC), while Y2-receptors may inhibit the intracellular release process with a mechanism independent of the calcium entry.

4-Aminopyridine↗
PubMed1994

Effects of benazepril on stress testing blood pressure in essential hypertension.

The effects of different doses of the angiotensin-converting enzyme inhibitor benazepril on cardiovascular response to a set of standardized laboratory tasks were analyzed. Eighteen patients (15 men and 3 women) with mild-to-moderate essential hypertension were randomly allocated to receive 10 or 20 mg of benazepril, or placebo, each administered once daily for 2 weeks, according to a double-blind, 3-period design. At the end of each treatment period, patients were examined at resting baseline and while performing mental arithmetic, handgrip and cycle ergometry tests. In comparison with placebo, the average reductions in resting systolic blood pressure (BP) were 8.7 mm Hg (95% confidence intervals [CI] -15.2 to -2.1) with 10 mg of benazepril, and 7.8 mm Hg (95% CI -14.4 to -1.3) with 20 mg; the corresponding reductions in resting diastolic BP were 5.1 mm Hg (95% CI -8.7 to -1.4) and 6.8 mm Hg (95% CI -10.4 to -3.1) (all p < 0.05). During mental arithmetic, the reductions in systolic BP were 10.4 mm Hg (95% CI -17.4 to -3.4) with 10 mg of benazepril, and 13.8 mm Hg (95% CI -20.8 to -6.8) with 20 mg; diastolic BP was reduced by 4.5 mm Hg (95% CI -8.5 to -0.5) and 8.3 mm Hg (95% CI -13.2 to -4.3), respectively (all p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Platelet alpha 2-adrenoceptors and diurnal changes of platelet aggregability in hypertensive patients.

OBJECTIVE: To analyse whether platelets from hypertensive patients have an increased responsiveness to aggregating agents during morning hours and whether these changes might be related to concurrent changes in platelet membrane alpha 2-adrenoceptor characteristics, plasma catecholamine and cortisol levels, and blood pressure values. DESIGN AND METHODS: Blood samples from 14 mild-to-moderate essential hypertensive males were collected in the morning (0700-0900 h) and the evening (1900-2100 h) to determine platelet aggregability responses to adrenaline and ADP, platelet alpha 2-adrenoceptor number and binding affinity to [3H]-yohimbine, plasma catecholamines and cortisol. During the same day patients underwent 24-h ambulatory blood pressure monitoring. RESULTS: The lowest concentration of adrenaline required to induce biphasic aggregation was significantly lower in the morning than in the evening, indicating an increased morning platelet aggregability to adrenaline; the minimum ADP concentration inducing aggregation was similar in morning and evening samples. There were no significant differences between morning and evening samples in platelet alpha 2-adrenoceptor number and binding affinity. Plasma adrenaline, noradrenaline and cortisol levels were higher in the morning than in the evening, but no correlation was observed between hormonal changes and the morning increase in platelet sensitivity to adrenaline. Ambulatory blood pressure recording showed abrupt morning elevations in systolic and diastolic blood pressures over sleeping values. However, morning blood pressure readings were not significantly different from those recorded during the rest of the day and in the evening. The morning rise in mean arterial pressure displayed a significant inverse correlation with the increased platelet sensitivity to adrenaline that was observed during the same hours. CONCLUSIONS: The results indicate that the increased morning responsiveness to adrenaline that was observed in platelets obtained from hypertensive patients does not appear to be mediated by changes in the characteristics of platelet membrane alpha 2-adrenoceptors, but morning blood pressure elevations might play some role in inducing this platelet hyper-reactivity.

Adenosine Diphosphate↗
PubMed1993

Region-specific inhibition of potassium-evoked [3H]noradrenaline release from rat brain synaptosomes by neuropeptide Y-(13-36). Involvement of NPY receptors of the Y2 type.

The effects of the Y2 receptor agonist neuropeptide Y NPY-(13-36) on the depolarization-evoked release of [3H]noradrenaline (NA) from synaptosomal preparations of the medulla oblongata, the hypothalamus, the hippocampal formation and the parieto-occipital cortex of the male rat were studied. NPY-(13-36) (0.1-100 nM) caused a concentration-related inhibition of the depolarization-induced release of [3H]NA in all areas studied, except the parieto-occipital cortex. The results indicate that NPY Y2 receptors are present on NA terminals in all areas studied, except the parieto-occipital cortex and inhibit depolarization-evoked [3H]NA release.

Animals↗
PubMed1990

A discrepancy between platelet alpha 2-receptor density and functional circulatory changes in hypertensives.

To investigate whether differences exist in peripheral alpha 2-adrenoceptors between normotensive and hypertensive subjects, we determined platelet alpha 2-adrenoceptor density in 10 (7 males) untreated essential hypertensives (mean age of 51.1 years, range of 44-59 years) and in 10 age- and sex-matched normotensive controls. Moreover, in hypertensive patients, we examined the relationship between receptor density and cardiovascular reactivity to mental arithmetic, static handgrip, and bicycle exercise, to verify the hypothesis that alpha 2-adrenoceptors might play a role in modulation of hemodynamic response to sympathetic stimuli. alpha 2-Adrenoceptor density, as calculated by binding of [3H]yohimbine to platelets, was significantly higher in essential hypertensives (314.8 +/- 38.7 fmol/mg) than in normotensive subjects (213.6 +/- 34.7 fmol/mg) (p less than 0.05), whereas receptor affinity was similar in both groups (4.0 +/- 0.5 nM hypertensives, 4.3 +/- 0.5 nM normotensives; p greater than 0.05). Mental arithmetic increased mean arterial pressure (MAP) by 21.5% from basal values and heart rate (HR) by 13.2%. During isometric exercise, MAP increased by 38.1% and HR by 24.7%, while during bicycle ergometry, mean increases in MAP and HR from baseline were of 27.2 and 54.3%, respectively. No correlation was found between platelet alpha 2-adrenoceptor density and percent changes in MAP induced by all tests, or between adrenoceptors and absolute basal and peak MAP values. Our findings suggest that in hypertensive patients, peripheral alpha 2-adrenoceptors are increased with respect to matched normotensives, but these receptors seem not to be involved in the modulation of cardiovascular adaptation to enhanced sympathetic activity.

Adult↗
PubMed1989

Heart rate variability and ventricular ectopic activity in hypertensive patients.

In order to investigate whether the severity of ventricular ectopic beats in hypertensive patients is influenced by the autonomic drive to the heart, we evaluated the relationship between the degree of dysrhythmias and 24-h spontaneous heart rate variability, an index of sympatho-vagal balance at cardiac level. Ambulatory 24-h ECG monitoring was used to examine 42 untreated essential hypertensives, previously scored for the presence and the extent of hypertensive target organ damage. No significant difference was found in the prevalence of complex ventricular ectopic beats in patients with a heart rate variability that was lower and higher than the arbitrary cut off points selected to divide subjects into groups. Neither heart rate variability nor the degree of arrhythmias was correlated with blood pressure levels, whereas the degree of ectopy was influenced by the presence of target organ damage and left ventricular hypertrophy (by ECG). Our results seem to exclude an association between dysrhythmias in hypertensives and autonomic outflow to the heart as detected by the analysis of heart rate variability.

Adult↗