Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of the antihypertensive agent, clonidine, was studied in a perfused preparation of rabbit middle cerebral arteries (MCA) in vitro. The MCA segments (8 mm long) were perfused at constant flow, the perfusion pressure upstream being monitored as an index of smooth muscle tone. In both normal (K+ = 2.7 mM) and high potassium (K+ = 30 mM) solutions, clonidine (3.10(-10) - 10(-4) mol.l-1) relaxed the arteries in a concentration-dependent manner. Expressed as a percentage of the maximum relaxation obtained in normal and high K+ solution with 10(-4) mol.l-1 papaverine, the Em was 79 +/- 3.9% (mean +/- SEM) and 63.7 +/- 2.4% respectively, and the EC 50 (4.3 +/- 2.0) 10(-8) mol.l-1 and (1.3 +/- 1.0) 10(-8) mol.l-1 respectively. The action of 6 specific antagonists at 3.10(-6) mol.l-1 was tested on the relaxation obtained in high potassium solution. The concentration-response curve was shifted to the right in a parallel manner, compatible with competitive inhibition, only by the H2-antagonist, cimetidine. Phentolamine and especially propranolol depressed the Em, suggesting antagonism by non-specific mechanisms. Methysergide and sulpiride induced no significant change in Em, but slightly displaced the curve in a nonparallel manner. Yohimbine had no effect on the relaxation. These results are interpreted as indicating that clonidine relaxes rabbit cerebral arteries in vitro, even at low, therapeutic concentrations, possibly by acting on H2-histaminergic receptors.
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PMID:Relaxation of rabbit cerebral arteries in vitro by clonidine. Evidence of H2-receptor mediation. 613 84

We have investigated in normal subjects the possible role of plasma free fatty acids (FFA) and blood ketone bodies (KB) in the regulation of human somatostatin secretion. Heparin injected during the intravenous infusion of a fat emulsion raised FFA levels acutely from 0.4 +/- 0.1 to near 3 mmol/L. Plasma somatostatin-like immunoreactivity (SLI) rose from a mean (+/- SEM) basal value of 9.2 +/- 1.0 ng Eq S14/L to 20.0 +/- 6.0 ng Eq S14/L (P less than 0.05). Plasma immunoreactive insulin (IRI) level was unchanged and glucagon (IRG) concentration decreased from 156 +/- 20 to 107 +/- 2 ng/L (P less than 0.05). During this test, there was a rise not only in FFA but also in plasma triglycerides (TG) and in blood glycerol and KB levels. The infusion of a fat emulsion alone increased triglyceride and glycerol levels to a similar extent but induced also a mild rise of FFA (0.37 +/- 0.05 to 1.13 +/- 0.5 mmol/L, P less than 0.01), KB (78 +/- 12 to 360 +/- 45 mumol/L, P less than 0.01), and SLI (14.8 +/- 4.6 to 23.8 +/- 7.1 ng Eq S14/L, P less than 0.05). The induction by DL-Na-3-hydroxybutyrate infusion of a rise of KB was associated with a decrease of FFA (P less than 0.05) and SLI (P less than 0.05) without modification of IRI or IRG levels. Phentolamine infusion did not modify the SLI or glucagon response to acute elevations of FFA, whereas propranolol suppressed the increase of SLI without preventing the concomitant decrease of IRG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of somatostatin secretion in man: study of the role of free fatty acids and ketone bodies. 614 47

We studied the effects of intense sympathetic stimulation on the chronotropic responses of the heart to subsequent test stimulations of the cardiac autonomic nerves in dogs anesthetized with alpha-chloralose. Such intense sympathetic stimulations (which we refer to as "release stimulations") are known to release neuropeptide Y as well as norepinephrine. The changes in cardiac cycle length evoked by vagal and sympathetic test stimulations were progressively more attenuated as we increased the frequency and duration of the antecedent sympathetic release stimulations. We found that 2.5 minutes after a maximal release stimulation (30 Hz for 5 minutes), the mean +/- SEM chronotropic responses to the vagal and sympathetic test stimulations were diminished to 36.5 +/- 1.6% and 54.7 +/- 1.3% respectively, of the prestimulation responses. The mean times for the chronotropic responses to the vagal and sympathetic test stimulations to recover to their control values were 52.0 +/- 1.3 and 63.2 +/- 2.9 minutes, respectively. This enduring effect suggests the action of a neuropeptide, such as neuropeptide Y. Phentolamine potentiated the inhibitory effects of the sympathetic release stimulations. The chronotropic responses to isoproterenol infusions were not affected appreciably by antecedent sympathetic release stimulation. We conclude, therefore, that the inhibitory effects of antecedent sympathetic release stimulation on cardiac sympathetic neurotransmission are mediated prejunctionally, probably via an inhibition of the neuronal release of norepinephrine by neuropeptide Y.
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PMID:Effects of intense antecedent sympathetic stimulation on sympathetic neurotransmission in the heart. 838 Feb 60

A release of radio-immunoassayable LHRH from the stalk-median eminence of neonatal piglets and prepubertal gilts was measured using an in vitro incubation system. The stalk-median eminence was collected from one-week-old male (n = 19) and female (n = 21) piglets and from 6-month-old prepubertal ovariectomized gilts given oestradiol benzoate (20 micrograms/kg b.w.; n = 52) or left untreated (control; n = 25) 30 or 68 h before slaughter. Each vial, containing the stalk-median eminence in 2 ml of Krebs-Ringer bicarbonate buffer, was incubated for 30 min, followed by 30 min incubations during which either basal release or the effect of adrenoreceptor antagonists and agonists on LHRH output was evaluated. There were no differences between the basal release of LHRH (x +/- SEM; pg/ml) from the stalk-median eminence of male (65.5 +/- 9.8) and female (66.3 +/- 9.6) newborn piglets. The addition of propranolol (10(-6) M) caused a 250% increase in LHRH release from the stalk-median eminence explants of neonatal males (p = 0.08) and females (p < 0.05). Neither norepinephrine nor phentolamine affected LHRH release from the stalk-median eminence of newborn males and females. The basal release of LHRH (pg/ml) from the stalk-median eminence explants collected from ovariectomized gilts given oestradiol benzoate 30 and 68 h before slaughter or left untreated was similar (147.5 +/- 36.1, 236.4 +/- 77.7 and 202.0 +/- 41.6, respectively). Propranolol evoked a significant increase in LHRH secretion from the stalk-median eminence in the control group, but not in the groups given oestradiol benzoate. Norepinephrine (10(-6) M) increased LHRH release from the stalk-median eminence collected from the control animals, 30 h and 68 h after oestradiol benzoate treatment by 48, 78 and 73 percent, respectively. Phentolamine (10(-6) M) did not affect LHRH release from the stalk-median eminence in control animals and ovariectomized gilts primed with oestradiol benzoate. Urapidil (10(-6) M, alpha 1-adrenoreceptor antagonist) did not affect the basal LHRH release from the stalk-median eminence of gilts from the control group and group slaughtered 30 h after oestradiol benzoate treatment, but caused a rapid increase of LHRH release from the stalk-median eminence 68 h after oestradiol benzoate treatment. Phenylephrine (10(-6) M) did not affect LHRH output from the stalk-median eminence collected at various time periods after oestradiol benzoate administration in vivo. These results suggest that in pigs, nerve terminals releasing LHRH at the stalk-median eminence level are sensitive to adrenergic stimulation or inhibition and that the adrenergic system can be modulated by estrogens in the prepubertal gilts.
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PMID:The effect of adrenoreceptor antagonists and agonists on LHRH release from the stalk-median eminence in the pig. 953 Apr 36

We investigated the relationship between changes in small intestinal motility and changes in blood pressure and heart rate in response to intestinal distension. Rats were maintained under stable anaesthesia with alpha-chloralose, and jejunal motility, blood pressure and heart rate were recorded. Pressure changes during propagated contractions of the circular muscle were recorded in the jejunum when the intraluminal pressure was maintained at 10 mmHg. Raising the pressure in 10 mmHg increments from 10 mmHg to 40 mmHg increased the frequency of propagated contractions from 0.30 +/- 0.06 min-1 (mean +/- SEM) to 1.29 +/- 0.09 per min. In contrast, amplitudes of contractions above baseline pressure decreased from 19.5 +/- 0.6 mmHg to 7.8 +/- 0.5 mmHg. Simultaneously, blood pressure and heart rate were both increased. Pretreatment of rats with capsaicin, or severing the mesenteric nerves acutely, prevented these cardiovascular responses, but did not influence the changes in propagated activity caused by distension. Propagated contractions were blocked by hexamethonium (10 mg kg-1, intravenously [i.v.]) and by local application of 2% lidocaine, but propulsion was unchanged by hyoscine (1 mg kg-1, i.v.). Phentolamine (1 mg kg-1, i.v.) increased the frequency of propagated contractions. The methods described in this work allow the effects of drugs on intrinsic intestinal reflexes to be distinguished from their effects on extra-intestinal, pseudoaffective reflexes. In addition, unlike other experiments using anaesthetized rats, blood pressure increased in response to distension, as it does in mammals that are not anaesthetized. The experiments demonstrate that the neural pathways for propagated contractions that rely on intrinsic nerve circuits, including intrinsic primary afferent neurones, and the neural pathways for extrinsic reflexes that signal pain or discomfort in the intestine, which involve capsaicin-sensitive spinal afferent neurones, are independent.
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PMID:The relationship between propagated contractions and pseudoaffective changes in blood pressure in response to intestinal distension. 1190 18