Biomedical subjects

S N Yang

Publications and source records attributed to S N Yang.

At least 55 records · Page 3Linked to original sources

PubMed1996

The non-peptide neuropeptide Y Y1 receptor antagonist BIBP3226 blocks the [Leu31,Pro34]neuropeptide Y-induced modulation of alpha 2-adrenoceptors in the nucleus tractus solitarii of the rat.

The potential blockade of the neuropeptide Y (NPY) Y1 receptor agonist [Leu31,Pro34]NPY-induced modulation of the characteristics of alpha 2-adrenoceptor agonist [3H]p-aminoclonidine binding sites by a selective non-peptide NPY Y1 receptor antagonist BIBP3226, was studied in the nucleus tractus solitarii of the rat by means of quantitative receptor autoradiography. [Leu31,Pro34]NPY at a concentration of 10 nM significantly increased the Kd value of [3H]p-aminoclonidine binding sites in the nucleus tractus solitarii without influencing the Bmax, suggesting the existence of an antagonistic modulation by NPY Y1 receptors of alpha 2-adrenoceptors in the nucleus tractus solitarii. BIBP3226 at 100 nM fully blocked the [Leu31,Pro34]NPY-induced increase in Kd of the [3H]p-aminoclonidine binding sites. The present results therefore provide evidence, by use of a NPY Y1 receptor antagonist, for the existence of a NPY Y1/alpha 2 receptor interaction in the nucleus tractus solitarii.

Animals↗

PubMed1996

Localization of neuropeptide Y Y1 receptor-like immunoreactivity in catecholaminergic neurons of the rat medulla oblongata.

Neuropeptide Y receptors in the medulla oblongata participate in central cardiovascular control. The neuropeptide Y1 receptor subtype gene and amino acid sequence have been identified by molecular cloning studies. In this study, a C-terminal peptide representing amino acids 355-382 of the neuropeptide Y1 receptor was synthesized and cross-linked to thyroglobulin to produce an antibody against a partial sequence of the neuropeptide Y1 receptor, used to localize neuropeptide Y1 receptor-like immunoreactivity in the catecholaminergic neurons of the medulla oblongata. The double colour immunofluorescence technique with a polyclonal antibody against the neuropeptide Y1 receptor and a monoclonal antibody against tyrosine hydroxylase revealed that in the rat medulla oblongata, a weak (the C3 cell group) to moderately intense (the A1, A2, C1 and C2 cell groups), diffuse cytoplasmic neuropeptide Y1 receptor-like immunoreactivity was distributed primarily in the noradrenergic and adrenergic cell bodies and occasionally seen in the noradrenergic and adrenergic cell processes. Almost all tyrosine hydroxylase-like immunoreactive cell bodies in the A1, A2, C1, C2 and C3 cell groups showed neuropeptide Y1 receptor-like immunoreactivity. The neuropeptide Y1 receptor-like immunoreactivity in the A2 cell group was somewhat stronger. The present findings show localization of specific neuropeptide Y1 receptor-like immunoreactivity in the vast majority of the noradrenergic and adrenergic cell bodies of the A1, A2, C1, C2 and C3 cell groups, which are putative cardiovascular regions. The results support the view that neuropeptide Y1 receptors in the medulla oblongata are involved in central cardiovascular control and may coexist with another important receptor, the alpha 2A-adrenoceptor, also involved in central, cardiovascular regulation, since the alpha 2A-adrenoceptor-like immunoreactivity has been shown to exist in almost all noradrenergic and adrenergic cell bodies in the brainstem. In conclusion, centrally administered neuropeptide Y may act in part via neuropeptide Y1 receptors located on the soma and dendrites of noradrenergic and adrenergic neurons, where it may interact with alpha 2-adrenoceptors at least in the noradrenergic A2 neurons. This noradrenaline system may be involved in at least part of the vasodepressor actions of neuropeptide Y, noradrenaline and adrenaline in the nucleus tractus solitarii in view of the present findings.

Animals↗

PubMed1995

Evidence for a differential modulation of the alpha-2 adrenoceptors by angiotensin II in the nucleus tractus solitarii of the spontaneously hypertensive and the Wistar-Kyoto normotensive rats.

An interaction between angiotensin II (Ang II) receptors and alpha 2-adrenoceptors was evaluated in the nucleus tractus solitarii (NTS) of the normotensive Wistar-Kyoto rat (WKY) and of the spontaneously hypertensive rat (SHR) using quantitative receptor autoradiography and cardiovascular analysis. In the WKY rat, Ang II promoted a dose-dependent increase in the IC50 value of l-noradrenaline when competing for ([3H]p-aminoclonidine ([3H]PAC) binding sites, which reached a maximum of 400% with 10 nM of Ang II and was associated with a small decrease in the B0 value (20%). In the SHR Ang II (0.1 nM) had an opposite effect leading to a decrease in the IC50 value of about 57%, and no change was observed in the B0 value. Saturation analysis also showed that Ang II (0.1 nM) increased the KD value of [3H]PAC in the WKY strain but in contrast decreased the KD value of [3H]PAC in the SHR. The Bmax value was not significantly changed neither in the WKY rat nor in the SHR. The cardiovascular analysis showed that a threshold dose of Ang II (0.05 pmol) counteracted the vasodepressor effect produced by l-noradrenaline coinjected in the NTS of the WKY rat. No effect was observed in heart rate. In the SHR no counteraction of the l-noradrenaline-induced vasodepressor effect was found, and in contrast a slight increase of the vasodepressor effect associated with a significant increase in the bradycardiac response was observed. The results give evidence for an antagonistic Ang II/alpha 2 receptor interaction in the cardiovascular part of the NTS of the WKY rat as previously observed in the Sprague-Dawley rat. However, this interaction is altered in the SHR, so that in this strain the Ang II/alpha 2 receptor interaction enhances alpha 2 affinity and possibly alpha 2 receptor function. This opposite effect observed in the SHR may represent one compensatory mechanism to counteract the development of high blood pressure in the SHR.

Angiotensin II↗

PubMed1995

Counteraction of NYP-induced c-Fos expression in the nucleus tractus solitarii by alpha 2 receptor agonists.

Neuronal c-Fos protein-like immunoreactivity (c-Fos IR) in parts of the nucleus tractus solitarii (NTS)-dorsal motor nucleus of the vagus nerve (dmnX) complex of the anaesthetized rat was studied 90 min after NTS microinjections of neuropeptide Y (NPY) and/or adrenergic receptor agonists in relevant cardiovascular doses. Microinjections of NPY and l-adrenaline alone into the NTS induced neuronal c-Fos IR in parts of the NTS-dmnX complex, while clonidine had no action. No double-labelled GFAP/c-Fos immunoreactive cells were found in the NTS-dmnX complex after the microinjection of NPY into the NTS. Coinjections of NPY and l-adrenaline or clonidine into the NTS reduced the NPY-induced increase in c-Fos IR. The results emphasize that during cardiovascular regulation NPY receptors can control neuronal gene expression in the NTS-dmnX complex via c-fos and that stimulation of alpha 2-adrenoceptors can attenuate NPY receptor transduction also in terms of induction of c-Fos IR in the NTS-dmnX complex via an antagonistic alpha 2/NPY receptor interaction.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1995

Reduction of dopamine D2 receptor transduction by activation of adenosine A2a receptors in stably A2a/D2 (long-form) receptor co-transfected mouse fibroblast cell lines: studies on intracellular calcium levels.

A stably co-transfected mouse fibroblast cell line, which expresses the long form of the human dopamine D2 receptor and the dog adenosine A2a receptor, was used to analyse the mechanism underlying changes in the cytosolic free calcium concentration ([Ca2+]i) induced by activation of D2 (long-form) receptors and its modulation by the A2a receptor agonist CGS 21680 by means of fura-2 imaging. Quinpirole (1-1000 nM), a D2 receptor agonist, caused a concentration-dependent increase in [Ca2+]i. Haloperidol, a preferential D2 receptor antagonist, completely blocked this [Ca2+]i response to quinpirole. Preincubation with Ca(2+)-free medium containing 2 mM EGTA or a medium containing 320 mM ethanol, an inositol 1,4,5-triphosphate receptor antagonist, substantially diminished the increase in [Ca2+]i evoked by quinpirole. Furthermore, quinpirole totally failed to elevate [Ca2+]i in a medium containing both 2 mM EGTA and 320 mM ethanol. CGS 21680 (1-500 nM) did not, by itself, exert any significant effect on [Ca2+]i. However, 100 nM of CGS 21680 substantially counteracted the [Ca2+]i responses to quinpirole (10-1000 nM). Moreover, this counteraction still occurred after blocking Ca2+ mobilization from intracellular stores with ethanol, but disappeared when the cells were pretreated with the Ca(2+)-free medium containing 2 mM EGTA. Our findings imply that the D2 (long-form) receptors in the present fibroblast cell line can raise [Ca2+]i both via Ca2+ influx from the extracellular medium and Ca2+ release from intracellular stores via activation of inositol 1,4,5-triphosphate receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1994

Antagonistic regulation of alpha 2-adrenoceptors by neuropeptide Y receptor subtypes in the nucleus tractus solitarii.

The modulation of alpha 2-adrenoceptors by neuropeptide Y Y1 and neuropeptide Y Y2 receptor subtypes has been studied in the nucleus tractus solitarii of the male rat. The autoradiographical experiments showed that neuropeptide Y-(1-36), neuropeptide Y-(13-36), a selective neuropeptide Y Y2 receptor agonist, and [Leu31,Pro34]neuropeptide Y, a selective neuropeptide Y Y1 receptor agonist, in the nanomolar range increased the Kd value of the [3H]p-aminoclonidine binding sites in the above rank order of potency without changing the Bmax values. In contrast, in the competition experiments, the neuropeptide Y Y1 and the neuropeptide Y Y2 receptor agonists decreased and increased, respectively, with the same potency the IC50 value of l-adrenaline and especially of clonidine for the alpha 2-adrenoceptor agonist binding sites associated with an increase and a decrease of the B0 value, respectively. Cardiovascular experiments showed that microinjections of clonidine into the nucleus tractus solitarii induced dose-dependent vasodepressor and bradycardiac responses. Threshold doses for vasodepressor effects of neuropeptide Y-(1-36) and of the neuropeptide Y Y1 receptor agonist and for vasopressor effects of the neuropeptide Y Y2 receptor agonist significantly counteracted the vasodepressor action elicited by an ED50 dose of clonidine in the nucleus tractus solitarii, the bradycardiac action of clonidine also being counteracted by the neuropeptide Y Y2 but not the neuropeptide Y Y1 receptor agonist. The present results give indications for the existence of an antagonistic modulation of high affinity alpha 2-adrenoceptors by the neuropeptide Y Y1 and neuropeptide Y Y2 receptor subtype in the nucleus tractus solitarii which may contribute to a reduction of alpha 2-adrenoceptor-mediated cardiovascular depression.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed1994

Evidence for an antagonistic angiotensin II/alpha 2-adrenoceptor interaction in the nucleus tractus solitarii.

Interactions between alpha 2-adrenoceptors and angiotensin II receptors were evaluated in the nucleus tractus solitarii of the rat by means of quantitative receptor autoradiography and cardiovascular analysis. In binding experiments using l-noradrenaline to compete for [3H]p-aminoclonidine binding sites, angiotensin II (1 nM) increased the IC50 value of l-noradrenaline by 50%. The angiotensin AT1 receptor antagonist, DUP753 (losartan), not only blocked this action but also decreased the IC50 value of l-noradrenaline. The modulatory effect of angiotensin II was also evaluated after addition of both DUP753 and PD123319, an angiotensin AT2 receptor antagonist, and counteraction of the reduction in the IC50 value of l-noradrenaline was observed. In saturation experiments angiotensin II increased the KD and Bmax values of [3H]p-aminoclonidine binding sites, compatible with possible uncoupling of the alpha 2-adrenoceptors. Cardiovascular analysis demonstrated that a threshold dose of angiotensin II (0.05 pmol) counteracted the vasodepressor effect produced by an ED50 dose of l-adrenaline, l-noradrenaline or clonidine coinjected in the nucleus tractus solitarii. DUP753 fully blocked this in vivo modulation of alpha 2-adrenoceptors by angiotensin II. These findings suggest the existence of an antagonistic angiotensin AT1/alpha 2-adrenoceptor interaction in the nucleus tractus solitarii. Therefore, it can be surmised that the activation of angiotensin II AT1 receptors may reduce the transduction of the alpha 2-adrenoceptors and thus the alpha 2-mediated vasodepressor responses.

Adrenergic alpha-Antagonists↗

PubMed1994

Selective modulation of the NPY receptors of the Y2 subtype by alpha 2 receptors in the nucleus tractus solitarii of the rat. A cardiovascular and quantitative receptor autoradiographical analysis.

The modulation of neuropeptide Y (NPY) receptors by alpha 2 receptors in the nucleus tractus solitarii (Sol) of the rat was evaluated using quantitative receptor autoradiography and measurements of mean arterial blood pressure and heart rate. The receptor autoradiographical experiments showed that clonidine (10 nM), a selective alpha 2 receptor agonist, induced a 59% increase in the B0 value and a 47% decrease in the IC50 value of NPY(1-36) when competing for [125I]peptide YY ([125I]PYY)-binding sites in the presence of [Leu31, Pro34]NPY (100 nM), a selective NPY Y1 receptor agonist, to block the binding to NPY Y1 receptors. In contrast, when NPY(13-36) (300 nM), a selective NPY Y2 receptor agonist, was used to block the binding to NPY Y2 receptors, clonidine (1-30 nM) did not affect the B0 value and the IC50 value of NPY(1-36) when competing for [125I]PYY-binding sites, suggesting that the stimulation of alpha 2 receptors can selectively increase the affinity of NYP(1-36) for the NPY Y2 receptor. Microinjections of threshold doses of adrenaline or clonidine into the Sol not only counteracted the vasopressor action of a close to ED50 dose of coinjected NPY(13-36), but also changed the vasopressor and tachycardic response produced by NPY(13-36) into a vasodepressor and bradycardic response. However, threshold doses of adrenaline or of clonidine microinjected into the Sol did not modify the vasodepressor responses to a close to ED50 dose of NPY(1-36) or of [Leu31, Pro34]NPY.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Coinjections of NPY(1-36) or [Leu31,Pro34]NPY with adrenaline in the nucleus tractus solitarius of the rat counteract the vasodepressor responses to adrenaline.

The cardiovascular effects of adrenaline microinjected alone or together with neuropeptide Y (NPY) receptor agonists into the nucleus tractus solitarius (Sol) of the anaesthetized rat have been investigated in order to evaluate NPY/adrenergic receptor interactions. In the dose range 0.05-20 nmol, adrenaline microinjected unilaterally into the Sol produced significant dose-related reductions in mean arterial blood pressure and heart rate. The vasodepressor action of a close to ED50 dose of adrenaline (0.5 nmol) was significantly counteracted by a threshold dose of NPY (1-36) (1 pmol) and of the NPY Y1 receptor agonist [Leu31,Pro34]NPY (2.5 pmol) microinjected into the Sol, but not by a threshold dose of NPY(13-36)(50 fmol), a selective Y2 receptor agonist. The present study provides evidence for an antagonistic NPY Y1/adrenergic receptor interaction in the Sol of the rat, involved in cardiovascular regulation.

Animals↗

PubMed1993

Microinjections of subpicomolar amounts of NPY(13-36) into the nucleus tractus solitarius of the rat counteract the vasodepressor responses of NPY(1-36) and of a NPY Y1 receptor agonist.

Microinjections of neuropeptide Y (NPY) (1-36) and of the NPY Y1 agonist [Leu31,Pro34]NPY into the caudal dorsomedial part of the nucleus tractus solitarius (Sol) in the anaesthetized rat led to the development of dose-related vasodepressor and bradycardic responses. The threshold dose of the NPY Y2 agonist NPY(13-36) (50 fmol) significantly counteracted the vasodepressor actions of a close to ED50 dose of NPY(1-36) (2.5 pmol) and of the NPY Y1 agonist (5 pmol). These results indicate that NPY Y1 receptor activation in the Sol leads to the development of a vasodepressor response, which can be counteracted by NPY Y2 receptor activation in the Sol. The results support the existence of a Y2/Y1 receptor-receptor interaction in the Sol, via which NPY Y2 receptors may reduce transduction over NPY Y1 receptors.

Animals↗

PubMed1993

Effects of histamine on intracellular Na+ activity and twitch tension in guinea pig papillary muscles.

Effects of histamine on the twitch tension, intracellular Na+ activity (aiNa), and action potential were simultaneously and continuously measured in the isolated cardiac papillary muscle of guinea pigs. In the driven fiber at 60 beats/ min, histamine induced a concentration-dependent positive inotropic effect, and apparently increased the amplitude of the action potential and shortened the duration at 3 microM, and significantly decreased aiNa by 6.7% from the control value of 4.5 +/- 0.1 mM (n = 6, p < 0.05) at 0.3 microM. Cimetidine at 10 microM did not produce any significant effect but partially antagonized the action of histamine. The respective concentrations of 1 and 3 microM histamine significantly decreased aiNa by 5.4 and 14.3% from the control 5.6 +/- 0.1 mM (n = 6, p < 0.05) in the presence of 10 microM cimetidine. Chlorpheniramine at 10 microM significantly reduced the twitch tension and aiNa, and prolonged the action potential duration. Histamine at 1 microM increased the twitch tension and decreased aiNa from 4.5 +/- 0.1 to 4.1 +/- 0.1 mM (n = 5, p < 0.05) in the presence of 10 microM chlorpheniramine. The combined application of 10 microM cimetidine and 10 microM chlorpheniramine reduced the twitch tension and abolished most effects of histamine. In high potassium solution (16.2 mM), 1 microM histamine significantly decreased aiNa by 12.9% from the control of 3.1 +/- 0.2 mM (n = 5, p < 0.05). The treatment of 0.5 or 1 microM ouabain increased the tension development and aiNa, and abolished the decrease in aiNa produced by the effect of histamine. The results suggest that histamine can directly stimulate Na-K pump in sarcolemma through means of the activation of both H1- and H2-receptors.

Action Potentials↗

PubMed1993

[Hypotensive effect of neuropeptide Y in substantia nigra].

The central hypotensive effect of neuropeptide Y (NPY) has been investigated by microinjection of the peptide into substantia nigra (SN) of anesthetized normotensive rats. NPY microinjection into SN produced dose-dependent falls in arterial blood pressure but no change in heart rate statistically. Microinjection of cholecystokinin octapeptide or 0.9% saline into SN did not elicit prominent change in arterial blood pressure and heart rate. The results suggest that NPY in SN exerts a distinctive hypotensive effect in certain degree.

Animals↗

PubMed1992

[Cardiovascular effects of microinjection of neuropeptide Y into lateral septal nucleus].

Cardiovascular effects of microinjection of neuropeptide Y (NPY) into the lateral septal nucleus (LS) were investigated in anaesthetized rats. The microinjection gave rise to a significant increase in blood pressure and heart rate. The pressure response was dose-dependent but the tachycardia was not. Control injection of 0.9% saline into LS produced no haemodynamic response.

Animals↗

PubMed1992

Effects of neuropeptide Y injected into A1 noradrenergic nucleus on blood pressure and catecholamines in plasma of cats.

The microinjection of neuropeptide Y (NPY) 0.75 and 1.5 micrograms into A1 noradrenergic nucleus of cats produced dose-dependent falls in mean arterial blood pressure of 2.0 +/- 0.6 and 4.9 +/- 2.4 kPa, respectively. NPY microinjection (1.5 micrograms) also produced marked decreases in noradrenaline (5 +/- 4 pmol.ml-1) and adrenaline (23 +/- 8 pmol.ml-1), but no significant change in dopamine in blood plasma. The results suggest that the depressor effect of NPY in A1 noradrenergic nucleus may be realized by not only reducing the release of noradrenaline in sympathetic terminals around the peripheral vascular beds but also inhibiting the sympathetico-adrenal system.

Animals↗

PubMed1992

Effect of gluco- and mineralocorticoids on gene expression of atrial natriuretic peptide by rat atria in vivo.

The effect of gluco- and mineralocorticoids on atrial natriuretic peptide (ANP) gene expression as well as plasma sodium and potassium concentrations was studied in both intact and adrenalectomized Wistar rats. Atria total RNA was extracted with cold phenol method and hybridized to alpha-32P labeled rat ANP-cDNA probe. The ANP gene transcripts in intact rats receiving dexamethasone and in adrenalectomized rats receiving both dexamethasone and deoxy-corticosterone increased by twofold, while there were no significant changes in the other groups. There were no parallel correlations between the rise of corticoid hormones-induced plasma Na+ concentration and the enhancement of rANP-mRNA level. The results suggest that glucocorticoids, when used together with mineralocorticoids, may directly increase ANP gene expression, whereas administration of mineralocorticoids alone has no effect on ANP gene expression.

Adrenalectomy↗

PubMed1992

Cardiovascular effects of intracerebral injection of neuropeptide Y in rats.

Cardiovascular effects of microinjection of neuropeptide Y (NPY) (25, 50, and 100 pmol/site) into field CA3 of hippocampus (CA3), lateral septal nuclei (LSN) and substantia nigra (SN) were investigated in urethane-anesthetized rats. NPY administered into CA3 produced a dose-dependent hypotension and bradycardia. Maximal changes of mean arterial blood pressure (MAP) were -1.5 +/- 0.7, -2.0 +/- 0.4, and -4.2 +/- 1.6 kPa, respectively; maximal changes of heart rate (HR) were -7 +/- 14, -23 +/- 24, and -64 +/- 50 bpm, respectively. NPY microinjection into LSN produced a dose-dependent increase in MAP (0.9 +/- 0.8, 1.3 +/- 0.5, and 3.1 +/- 0.5 kPa, respectively) and a prominent increase in HR (14 +/- 15, 41 +/- 28, and 42 +/- 31 bpm, respectively), but the tachycardia was not dose-dependent. NPY applied into SN elicited a dose-dependent decrease in MAP (-1.0 +/- 0.5, -2.2 +/- 0.9, and -4.3 +/- 2.0 kPa, respectively), but no statistically significant change in HR. The results showed that exogenously applied NPY has distinct cardiovascular effects in CA3, LSN, and SN.

Animals↗

PubMed1992

[Cardiovascular effects of kainic acid injected into habenular nucleus].

The present study was to determine if the cardiovascular effect being produced by exciting cells in the habenular nucleus (Hab). Experiments were performed on urethane-anesthetized rats. Microinjection of kainic acid into Hab demonstrated dose-dependent increases in arterial blood pressure and heart rate, accompanied by other sympathetic reactions, such as mydriasis and pilo-erection. But microinjection of lidocaine into Hab did not elicit similar effects mentioned above.

Animals↗

PubMed1992

[Cardiovascular effect of norepinephrine in the habenular nucleus and the underlying mechanism in rats].

Cardiovascular effect of norepinephrine (NE) in the habenular nucleus (Hb) and the underlying mechanism were investigated in urethane-anesthetized rats. NE microinjection into Hb produced a dose-dependent increase in mean arterial blood pressure and heart rate, an effect that could be attenuated by the pretreatment in Hb with alpha-receptor blocker phentolamine, but not by the pretreatment with beta-receptor blocker propranolol or physiological saline. Microinjection of kainic acid into Hb gave rise to a marked increase in mean arterial blood pressure and heart rate, but microinjection of lidocaine did not elicit significant cardiovascular effect. The above results suggest that NE in Hb plays an important role in cardiovascular control as a result of Hb excitation through activation of alpha-receptor.

Animals↗