UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neural input to the frog bladder was characterized in vitro. The nerve-evoked bladder contraction consists primarily of an early parasympathetic cholinergic component and a later, longer-lasting non-adrenergic non-cholinergic component. This slow non-adrenergic non-cholinergic contraction is not only resistant to cholinergic and adrenergic antagonists, but also to H1 and H2 histaminergic antagonists and to the serotoninergic antagonist, methysergide. It is concluded that the non-adrenergic non-cholinergic contraction is mediated by an efferent action of the sensory system because it is resistant to ganglionic nicotinic antagonists and because it is elicited specifically by stimulation of the peripheral cut end of the dorsal root. 5-Hydroxytryptamine is a potent and specific inhibitor of the sensory non-adrenergic non-cholinergic contraction. Although the bladder smooth muscle is innervated by terminals containing a somatostatin-like substance, somatostatin does not cause a bladder contraction. Luteinizing hormone-releasing hormone, enkephalin, histamine, 5-hydroxytryptamine, adenosine and adenosine 5 monophosphate are also unlikely candidates for the non-adrenergic non-cholinergic transmitter because they do not produce bladder contractions and/or their antagonists are ineffective on the nerve-evoked contraction. A putatively sensory network of fibers containing a substance P-like material is located within the wall of the bladder. Substance P produces bladder contractions at concentrations as low as 10(-9) M and so it, or a related substance, is a viable transmitter candidate in this system. Adenosine 5'-triphosphate (ATP)(10(-5) M) also causes a bladder contraction and remains a possible candidate as well. The data demonstrate that the bladder contraction resulting from electrical stimulation of the bladder nerves is due in large part to the "antidromic" stimulation of sensory axons. The likely presence therefore of potent and releasable substances in the peripheral sensory terminals of the bladder suggests that this sensory system may exert significant local, efferent control of bladder smooth muscle (i.e. independent from the central nervous system).
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PMID:The efferent role of sensory axons in nerve-evoked contractions of bullfrog bladder. 244 35

Previous studies have shown that exposure of parotid acinar cells to substance P at 37 degrees C results in activation of phospholipase C, formation of [3H]inositol 1,4,5-trisphosphate (IP3), and persistent desensitization of the substance P response. In cells treated with antimycin in medium containing glucose, ATP was decreased to approximately 20% of control values, IP3 formation was completely inhibited, but desensitization was unaffected. When cells were treated with antimycin in the absence of glucose, cellular ATP was decreased to approximately 5% of control values, and both IP3 formation and desensitization were blocked. A series of substance P-related peptides increased the formation of [3H]IP3 and induced desensitization of the substance P response with a similar rank order of potencies. The substance P antagonist, [D-Pro, D-Trp]-substance P, inhibited substance P-induced IP3 formation and desensitization but did not induce desensitization. These results suggest that the desensitization of substance P-induced IP3 formation requires agonist activation of a P-type substance P receptor, and that one or more cellular ATP-dependent processes are required for this reaction. However, activation of phospholipase C and the generation of inositol phosphates does not seem to be a prerequisite for desensitization.
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PMID:Substance P receptor desensitization requires receptor activation but not phospholipase C. 245 23

1. We examined the possibility that the neuropeptide, galanin, may act as a transmitter in longitudinal muscle isolated from the rat ileum. 2. Galanin at nanomolar concentrations produced a phasic contraction with a concomitant increase in rhythmic activity. At concentrations in excess of 3 x 10(-8) M, the contraction was followed by a rapid desensitization; hence, with the cumulative re-addition of galanin, there was no response. This desensitization was probably selective for galanin because there was no attenuation of the contractile responses to substance P, neurokinin A and B, bradykinin or carbachol. 3. The phasic contraction induced by galanin was not inhibited by atropine, guanethidine, hexamethonium, naloxone, tetrodotoxin or [D-Pro2, D-Trp7,9]-substance P. 4. Electrical stimulation of intramural nerves at low frequencies (1-5 Hz) led to an augmentation of spontaneous rhythmic contractions, which were completely or partially inhibited by atropine. However, guanethidine, hexamethonium, naloxone, [D-Pro2, D-Trp7,9]-substance P and desensitization to galanin were without effect on the response to such electrical stimulation. 5. In contrast, transmural electrical stimulation at higher frequencies in the presence of atropine and guanethidine produced biphasic contractile responses with transient and slow components. The slow component was selectively attenuated by galanin desensitization. 6. The slow component induced by high frequency stimulation was markedly attenuated by repeated electrical stimulation at short intervals (2.5 min between 30 s trains). Following repeated stimulation, the contractile response to galanin was also attenuated. Thus, a cross-desensitization between the mediator of the slow component and galanin had to be considered. In contrast, responses to tachykinins and the transient component induced by electrical stimulation were without effect. 7. Somatostatin, vasoactive intestinal polypeptide and alpha,beta-methylene ATP were without effect on the tone of the muscle. Calcitonin gene-related peptide, neurotensin, gastrin-releasing peptide, neuropeptide Y and capsaicin produced either a transient arrest of the spontaneous rhythmic activity or a transient relaxation. 8. These results suggest that the slow component of the non-cholinergic non-adrenergic contraction, as induced by intramural nerve stimulation is apparently due to the endogenous release of galanin, presumably released from galanin-containing nerves in the rat ileum.
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PMID:Contribution of galanin to non-cholinergic, non-adrenergic transmission in rat ileum. 246 26

1. The effect of an acid extract of the carp intestinal bulb (ECI) on guinea-pig ileum longitudinal smooth muscle (GPLM) and carp intestinal bulb longitudinal smooth muscle (CIBLM) was examined. 2. ECI caused a concentration-dependent contraction of GPLM and CIBLM. This ECI-induced response was reduced by atropine to 30-40% of the control, indicating that part of the contracting activity of ECI is attributable to acetylcholine. The atropine-resistant contracting activity of ECI was not mediated by histamine, 5-hydroxytryptamine, ATP, ADP, angiotensin II, neurotensin, vasoactive intestinal peptide or an opioid peptide. 3. The active material mediating the atropine-resistant contracting activity is probably a peptide, because the contraction in response to ECI was abolished on incubation with pepsin or alpha-chymotrypsin. 4. [D-Pro2, D-Trp7,9]-substance P, [D-Pro4, D-Trp7,9]-substance P (4-11) decreased the atropine-resistant contracting activity of ECI as did desensitization induced by substance P. 5. On a Sephadex G 25 column, the active material was eluted as one peak. The active fractions were pooled and then applied to another Sephadex G25 column to compare the Ve/Vo value for the active material with those for peptides of known molecular weights. The molecular weight of the active material was estimated to be 1200-1700 (1410 +/- 70, n = 6). 6. The results indicate the presence of a substance P-like peptide in the carp intestinal bulb.
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PMID:Presence of a substance P-like peptide in an acid extract of the intestinal bulb of the carp (Cyprinus carpio). 246 88

Endothelial cells are known to contain both soluble and particulate guanylate cyclase, but the functional role of cyclic guanosine monophosphate (cGMP) in endothelial cells remains unknown. We have investigated the effects of 8-bromo-cGMP on endothelium-dependent relaxations to acetylcholine, substance P, ATP, and the calcium ionophore A23187, and on endothelium-independent relaxations to sodium nitroprusside and glyceryl trinitrate (GTN). The ability of each of these agents to relax phenylephrine-preconstricted rings of rabbit aorta was tested in the absence and presence of 8-bromo-cGMP. In the presence of 8-bromo-cGMP, a greater concentration of phenylephrine had to be used to produce a similar level of tone and then endothelium-dependent relaxations to acetylcholine and substance P were inhibited, whereas endothelium-dependent relaxations to ATP and A23187 were unaffected. Endothelium-independent relaxations to sodium nitroprusside and GTN were only inhibited at the highest concentrations of nitroprusside and GTN. These results suggest that: (a) increasing GMP levels in endothelial cells inhibit agonist-induced release of endothelium-derived relaxing factor (EDRF); (b) a negative feedback mechanism may exist whereby EDRF stimulates soluble guanylate cyclase in endothelial cells to inhibit its own release; and (c) ATP does not induce EDRF release via phosphoinositol hydrolysis.
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PMID:Release of endothelium-derived relaxing factor is inhibited by 8-bromo-cyclic guanosine monophosphate. 246 85

The tridecapeptide neurotensin (NT) is present at high concentrations within the mammalian gut, although its physiological function is undefined. In this study, the actions of NT and structurally related peptides neuromedin N (NM-N) and xenopsin were characterized on ion transport in the porcine distal jejunal mucosa in vitro. The serosal-side administration of these peptides elicited rapid changes in transmural potential difference and short-circuit current (Isc) which were greater in mesenteric than in antimesenteric segments. NT-induced elevations in Isc were dependent upon external permeant anions and were associated with net Cl transport in both segments. In mesenteric segments, NT and its homologs increased Isc with the order of potency: NT greater than NM-N greater than xenopsin. NT produced tachyphylaxis to its own actions and to those of NM-N; NM-N was ineffective in producing tachyphylaxis. Isc elevations produced by NT were inhibited by the neuronal conduction blocker tetrodotoxin (0.1 microM) or the Ca++-channel blocker dl-verapamil (100 microM) and reduced in Ca++-free media. Antagonists to the enteric transmitters acetylcholine, ATP, 5-hydroxytryptamine, substance P and histamine did not alter Isc responses of mesenteric segments to NT. Serosal administration of vasoactive intestinal peptide (10 nM) did not resemble the effects of NT. The magnitude of Isc responses to these agonists was smaller in antimesenteric segments. These results indicate that NT-related peptides present in mucosal endocrine cells or nerves of the porcine jejunum may modulate Cl transport through mechanisms that involve the Ca++-dependent release of unknown enteric neurotransmitters. Moreover, there appear to exist within the distal jejunum circumferential differences in mucosal responses to NT and other neurohumoral factors.
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PMID:Neurohormonal regulation of ion transport in the porcine distal jejunum. Actions of neurotensin and its natural homologs. 246 65

Porcine or bovine endothelial cells cultured on microcarrier beads, packed into adapted chromatographic columns, perfused with Krebs' buffer and activated with appropriate stimuli (e.g. bradykinin, ADP or phospholipase C) release EDRF and prostacyclin into the perfusing fluid. In the effluent EDRF and prostacyclin might be bio-assayed using the Vane's superfusion cascade (rabbit aortic strips and bovine coronary artery strips, respectively) against nitroglycerine (GTN) and synthetic prostacyclin standards. Prostacyclin might be also quantified as 6-keto-PGF1 alpha by RIA. A spatial separation of the generator (endothelial cells) from the effector (vascular smooth muscle) has allowed to prove that EDRF is nitric oxide, that its activity is inhibited by superoxide anions and by chemicals which act via free radicals, finally, that the release of EDRF and prostacyclin is coupled by a receptor-mediated activation of phospholipase C. Although so successful, the above technique suffers from its essentials, i.e. from using cultured cells instead of fresh intact endothelial cells. Cultured endothelial cells are not responsive to many receptor agonists including acetylcholine, substance P and 5-hydroxytryptamine. Unlike fresh intact endothelial preparations the cultured cells which are perfused with Krebs' buffer generate superoxide anions at such concentrations that it might be obligatory infusing superoxide dismutase in order to detect EDRF. Nonetheless, a couple of data obtained with the cultured endothelial cells have been reproduced in the fresh cell preparations, e.g. release of EDRF by ADP and ATP, a coupled release of EDRF and prostacyclin by phospholipase C or a paradoxical augmentation of the sodium-nitroprusside-induced vasorelaxation by methylene blue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelium-derived relaxing factor (EDRF) from cultured and fresh endothelial cells. 247 Mar 61

1. The effects of capsaicin, calcitonin gene-related peptide and substance P were studied via three parameters in the guinea-pig vas deferens: the overflow of ATP and of tritiated noradrenaline, the mechanical responses to field stimulation and the mechanical responses to exogenous noradrenaline and alpha, beta-methylene ATP. 2. At 2 Hz, capsaicin inhibited the stimulus-evoked release of ATP, whereas it was without effect on the release of noradrenaline. At 20 Hz capsaicin did not affect the release of either of the cotransmitters. Capsaicin enhanced responses to alpha, beta-methylene ATP, but not to exogenous noradrenaline. 3. Calcitonin gene-related peptide, like capsaicin, inhibited the release of ATP, but not noradrenaline at 2 Hz and was without effect on release at 20 Hz. However, calcitonin gene related peptide inhibited responses to alpha, beta-methylene ATP and was without effect on responses to exogenous noradrenaline. 4. Substance P had no effect on the release of either noradrenaline or ATP at either frequency. However, like capsaicin it enhanced responses to alpha, beta-methylene ATP and was without effect on exogenous noradrenaline. 5. These results suggest that the actions of capsaicin on the guinea-pig isolated vas deferens are mediated via the release of both calcitonin gene-related peptide and substance P. Furthermore, as capsaicin and calcitonin gene-related peptide prejunctionally modulate purinergic, but not noradrenergic transmission, this suggests that the mechanisms for the storage and release of the sympathetic co-transmitters noradrenaline and ATP may not be the same.
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PMID:Modulation of neurotransmission in the guinea-pig vas deferens by capsaicin: involvement of calcitonin gene-related peptide and substance P. 247 44

A sympathetic neurone blocking drug, guanethidine, and a tachykinin antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP), partially inhibited the contractile response to nicotine to the same degree in the isolated detrusor strips of guinea-pig urinary bladder. Application of rpwwL-SP completely abolished the inhibitory effect of guanethidine on the nicotine-induced contraction, suggesting that the tachykinin(s)-ergic transmission might be involved in the sympathomimetic effect of nicotine. Conversely, when the preparation was treated with guanethidine to block release of a mediator from the sympathetic nerve, the inhibitory effect of rpwwL-SP was diminished, suggesting an exclusive contribution of the sympathetic nerve communications to the action of the tachykinin(s). We previously suggested that nicotine may release acetylcholine and ATP to contract the detrusor strips, and that acetylcholine output may be increased by an unknown substance released from the sympathetic nerve by nicotine. In preparations treated with atropine, rpwwl-SP had no effect on the nicotine-induced contraction. The concentration-response curves for carbachol and ATP were not influenced by rpwwl-SP. After tachyphylaxis to capsaicin developed, the nicotine-induced contraction was not affected. It is suggested that in guinea-pig detrusor, tachykinin(s) from capsaicin-insensitive sites is (are) involved in the excitatory sympathomimetic effect of nicotine, and that the tachykinin(s) behave(s) as a modulator finally to increase the acetylcholine output from the parasympathetic cholinergic nerve.
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PMID:Mechanism of action of nicotine in isolated urinary bladder of guinea-pig: involvement of tachykinin(s) released by nicotine in the drug's sympathomimetic effect. 248 45

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

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