Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypothalamic cAMP and cGMP levels in ovariectomized rats were evaluated after intravenous (IV) pulse injection and/or intraventricular (IVT) injection of substance P and/or neurotensin. Intravenous substance P lowered hypothalamic cAMP concentration whereas IVT injection of 2.5 micrograms substance P produced significant increase in cAMP levels. On the other hand, IV administration of neurotensin failed to alter hypothalamic cAMP levels while IVT injection induced significant decrease in cAMP. Intravenous pulse injection of substance P elevated hypothalamic cGMP levels while IVT injection decreased cGMP concentration. Hypothalamic cGMP concentration was not modified by IV administration of neurotensin. However, IVT injection of neurotensin significantly elevated cGMP levels. Since a number of neurotransmitters/neuropeptides exert their action through cyclic nucleotides the present results indicate differential responses of cAMP and cGMP to substance P and neurotensin and implicate a mediatory role for cAMP and cGMP in the neuroendocrine action of substance P and neurotensin.
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PMID:Differential responses of hypothalamic cAMP and cGMP to substance P and neurotensin in ovariectomized rats. 243 24

The localization and distribution of catecholamines, selected neuropeptides, and the cyclic nucleotide second messengers has been determined in the superior cervical ganglion of the stroke-prone variant of the spontaneously hypertensive rat (SHR) and its normotensive Wistar-kyoto (WKY) control. Significant alteration in the frequency of occurrence of dopaminergic small intensely fluorescent cell clusters was seen in the stroke-prone variant of the SHR. The immunofluorescent localization of cyclic AMP (cAMP) and cyclic GMP (cGMP) were also changed in the stroke-prone variant, as was the immunofluorescent staining quantity of the neuropeptides somatostatin and substance P. The morphological pattern of staining for the various compounds in the normotensive control (WKY) was equivalent to the Sprague-Dawley rat strain. The implications of the altered neurochemistry in the superior cervical ganglion on the high blood pressure, and the predisposition for stroke in this strain are discussed.
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PMID:Neurochemical differences in the superior cervical ganglion of the spontaneously hypertensive rat stroke-prone variant. 244 7

In epicardial conduit coronary artery strips obtained during autopsy within 2.5 h after death, relaxations induced by low concentrations of histamine were reversed to contractions by removal of endothelium, whereas those caused by bradykinin, substance P, and Ca2+ ionophore A23187 were almost abolished. In the artery strips with intact endothelium, which responded to histamine, bradykinin, and substance P with moderate or marked relaxations, acetylcholine elicited contractions. Endothelium denudation failed to potentiate the contractile response to acetylcholine and serotonin. Relaxant responses to histamine, bradykinin, and substance P did not significantly differ in coronary arteries from adults (35-48 yr old) and seniors (63-82 yr old). Two strips from a 2-mo-old male responded to acetylcholine only with contractions, and their responses to the vasodilators were not greater than those seen in the adult and senior arteries. Histamine increased guanosine 3',5'-cyclic monophosphate (cGMP); the increments did not differ in the arteries from adults and seniors. It may be concluded that endothelium is a major site for relaxant actions of histamine, bradykinin, and substance P, whereas muscarinic receptors, if any, in endothelium do not play an important role in the generation of relaxing factor from human coronary arteries. The endothelium-dependent relaxations do not appear to be altered with increasing age or in the arteries with slight atherosclerotic changes.
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PMID:Endothelium-dependent and -independent responses to vasoactive substances of isolated human coronary arteries. 247 41

Autoinhibition of acetylcholine release by the coexisting peptide galanin in the septal afferents to the hippocampus of the rat was examined in tissue slices from the hippocampus. Galanin inhibits the evoked release of the coexisting neurotransmitter, acetylcholine, in the ventral hippocampus, providing an example of autoinhibition of release of a neurotransmitter by one of the coexisting neurotransmitters. The galanin mediated inhibition of the acetylcholine release is a complement to the well known strong cholinergic autoinhibition. The effects of the coexisting galanin and acetylcholine on several second messenger systems were also examined: acetylcholine acting at muscarinic receptors depresses cyclic adenosine 3',5'-monophosphate and stimulates elevation of cyclic guanosine 3',5'-monophosphate levels, whereas neither cyclic adenosine 3',5'-monophosphate nor cyclic guanosine 3',5'-monophosphate levels were affected by galanin (1 microM). Galanin however inhibited partly the muscarinic stimulation of phosphoinositide breakdown, suggesting that inositol phosphate(s) or diacylglycerol may act as second messenger(s) of the galanin action in the hippocampus. The effects of chronic changes in firing rate on the coexisting neurotransmitters in the rat ventral spinal cord containing serotonin, thyrotropin releasing hormone, substance P and substance K were examined. The tissue levels of the coexisting transmitters were studied in rats chronically treated with imipramine (14 days; 2 x 10 mumoles/kg/day) and zimelidine (14 days; 2 x 10 mumoles/kg/day). Upon treatment with zimelidine the tissue levels of the serotonin metabolite 5-hydroxyindoleacetic acid fall by 32% while thyrotropin releasing hormone levels seem to increase 35% and substance P/substance K levels also increase 48 and 72% respectively. Imipramine treatment resulted in similar although less pronounced changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and chronic studies on functional aspects of coexistence. 248 72

A peptide derived from fibrinogen degraded by leukocyte elastase, and corresponding to amino acids 30-43 in the B beta-chain of fibrinogen, was evaluated concerning its effects on isolated bovine mesenteric arteries. This peptide induced dilation of the arteries and an increase in both cyclic AMP and cyclic GMP in the vessels. In addition there was an increase in 6-keto-PGF1 alpha indicating an increased release of prostacyclin. The increase in cyclic nucleotides and 6-keto-PGF1 alpha was inhibited by indomethacin, as was the vasodilation. The increase in cyclic GMP was much larger than the increase in cyclic AMP. The effects of the studied peptide are similar to the effects of other vasoactive peptides with a similar structure, such as bradykinin, neurotensin and substance P. The increase in cyclic AMP is probably caused by prostacyclin, a probable mediator of vasodilation. In addition, in certain species vasodilation may be caused by an increase in cyclic GMP.
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PMID:Effect of a peptide derived from fibrinogen degraded by leukocyte elastase on isolated bovine mesenteric arteries. 254 16

Endothelium-dependent relaxation of blood vessels is produced by a large number of agents (e.g., acetylcholine, ATP and ADP, substance P, bradykinin, histamine, thrombin, serotonin). With some agents, relaxation may be limited to certain species and/or blood vessels. Relaxation results from release of a very labile non-prostanoid endothelium-derived relaxing factor (EDRF) or factors. EDRF stimulates guanylate cyclase of the vascular smooth muscle, with the resulting increase in cyclic GMP activating relaxation. EDRF is rapidly inactivated by hemoglobin and superoxide. There is strong evidence that EDRF from many blood vessels and from cultured endothelial cells is nitric oxide (NO) and that its precursor is L-arginine. There is evidence for other relaxing factors, including an endothelium-derived hyperpolarizing factor in some vessels. Flow-induced shear stress also stimulates EDRF release. Endothelium-dependent relaxation occurs in resistance vessels as well as in larger arteries, and is generally more pronounced in arteries than veins. EDRF also inhibits platelet aggregation and adhesion to the blood vessel wall. Endothelium-derived contracting factors appear to be responsible for endothelium-dependent contractions produced by arachidonic acid and hypoxia in isolated systemic vessels and by certain agents and by rapid stretch in isolated cerebral vessels. In all such experiments, the endothelium-derived contracting factor appears to be some product or by-product of cyclooxygenase activity. Recently, endothelial cells in culture have been found to synthesize a peptide, endothelin, which is an extremely potent vasoconstrictor. The possible physiological roles and pathophysiological significance of endothelium-derived relaxing and contracting factors are briefly discussed.
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PMID:Endothelium-derived relaxing and contracting factors. 254 95

Binding of atrial natriuretic peptide (ANP) to rat submandibular gland and its effect on guanosine 3',5'-cyclic monophosphate (cGMP) formation and salivary secretion were investigated. Membranes rapidly and specifically bound 125I-ANP. Binding was inhibited by unlabeled ANP (IC50 approximately 1.6 nM), but not by atriopeptin I, other COOH- and NH2-terminal deleted ANP fragments, or agents such as pilocarpine or substance P. Scatchard analysis revealed a single class of high-affinity sites (dissociation constant 0.74 +/- 0.25 nM; maximal binding capacity 20.5 +/- 6.3 pmol/mg protein). Intravenous infusion of ANP with pilocarpine caused a significant dose-dependent increase in the levels of cGMP detected in plasma and saliva. Because salivary cGMP may have originated in plasma, the effect of ANP on cGMP formation was evaluated in dispersed cells. ANP evoked a concentration-dependent increase in both cGMP synthesis and secretion (EC50 approximately 1.7 x 10(-8) M). The atrial peptide did affect basal or l-isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate synthesis in dispersed cells. When infused by itself and/or with pilocarpine, ANP did not alter the rate of spontaneous or pilocarpine-induced salivary flow, secretion of chloride, or protein release. The data demonstrate the presence of guanylate cyclase-coupled ANP receptors in submandibular gland; the atrial peptide, however, does not exert an effect of the secretory function of the gland.
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PMID:Atrial natriuretic peptide stimulates submandibular gland synthesis and secretion of cGMP. 255 37

The objective of this study was to elucidate the mechanisms by which bradykinin and vasoactive intestinal polypeptide (VIP) relax bovine intrapulmonary artery and bradykinin, but not VIP, relaxes intrapulmonary vein. Bradykinin and VIP elicited entirely endothelium-dependent relaxation of phenylephrine-precontracted arterial rings, and this was associated with arterial accumulation of both guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP). Bradykinin, but not VIP, relaxed precontracted venous rings and increased cGMP, but not cAMP levels, by endothelium-dependent mechanisms. Neither arteries nor veins relaxed in response to substance P, thrombin, bombesin, arginine vasopressin, or angiotensin II. Methylene blue or indomethacin each partially antagonized, whereas both, when together, abolished arterial relaxant responses to bradykinin and VIP. Methylene blue or indomethacin, respectively, abolished arterial cGMP or cAMP accumulation elicited by bradykinin and VIP. Venous relaxation and cGMP accumulation elicited by bradykinin was abolished by methylene blue but was unaltered by indomethacin. Thus bradykinin and VIP relaxed bovine intrapulmonary artery by endothelium-dependent mechanisms involving the actions of cGMP and cAMP whose formation may be stimulated by endothelium-derived relaxing factor and prostacyclin, respectively. In contrast, bradykinin relaxed intrapulmonary vein by endothelium-dependent mechanisms involving only cGMP.
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PMID:Mechanisms of endothelium-dependent vascular smooth muscle relaxation elicited by bradykinin and VIP. 282 43

This study examined the effects of transmural nerve stimulation, acetylcholine, adrenoceptor agonists and several peptides on the contractility of strips of human gallbladder in vitro. Acetylcholine caused concentration-related contractions of the tissues and the sensitivity to acetylcholine was similar in gallbladders with mild and severe chronic cholecystitis. Noradrenaline and adrenaline relaxed gallbladder strips, probably via beta 2-adrenoceptor stimulation. Transmural nerve stimulation always caused contractions, but in the presence of atropine inhibitory responses were demonstrable and these were antagonized by propranolol. There was no evidence of non-adrenergic inhibitory neural responses. Of the peptides tested, only cholecystokinin octapeptide (CCK-OP), gastrin, pentagastrin, substance P and caerulein caused contractions. Responses to CCK-OP, gastrin and pentagastrin were antagonized by dibutyryl cyclic GMP. Hormones which had no effect upon human gallbladder strips included motilin, secretin, bombesin, neurotensin, glucagon, vasopressin, VIP and somatostatin. Considerable differences therefore exist between human tissues and those from experimental animals with respect to the direct actions of neural and hormonal stimuli on gallbladder contractility.
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PMID:Contractility of human gallbladder muscle in vitro. 297 88

A large number and variety of compounds (acetylcholine, adenosine diphosphate, adenosine triphosphate, arachidonic acid, bradykinin, Ca2+ ionophores, calcitonin gene-related peptide, histamine, hydralazine, substance P, thrombin, and vasoactive intestinal polypeptide) have been shown to relax arterial smooth muscle indirectly. The endothelium in muscular arteries from several species appears to have receptors for these vasodilators. Binding of one of these compounds to its endothelial receptors results in the release (and presumably synthesis) of substance(s) that act on arterial smooth muscle to cause relaxation. The name endothelium-derived relaxing factor (EDRF) has been proposed for the substance or substances responsible for inhibition of contraction. Studies to determine additivity of endothelium-dependent relaxing agents and sensitivity of EDRF-mediated responses to a variety of inhibitors suggest that a single factor or a single common mechanism induces relaxation of vascular smooth muscle. Pharmacological studies have been equivocal with regard to the postulated involvement of phospholipases or arachidonic acid and to the suggestion that EDRF is an oxidative, non-cyclooxygenase product of arachidonate. Experiments on transfer of EDRF and reversal of endothelium-dependent relaxation consistently indicate that EDRF is quite labile. There is convincing evidence that EDRF activates smooth muscle guanylate cyclase, which results in an increase in intracellular cyclic guanosine 3',5'-monophosphate levels. The stimulation of guanylate cyclase by EDRF provides a valuable and sensitive parameter for studies with arteries as well as cells in culture. At present, the identity of EDRF and its role in cardiovascular homeostasis are unknown.
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PMID:Endothelium-derived vascular relaxing factor. 298 29


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