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)

Supramaximal repetitive field stimulation with pulses of 50 microseconds produced contraction of strips of bladder from rabbits and guinea-pigs. Atropine reduced responses at all frequencies to about 60% and the contraction was poorly maintained. With the double sucrose-gap technique large excitatory junction potentials (e.j.p.s) were recorded with superimposed action potentials. These were not reduced by atropine or phentolamine. Substance P (SP) produced contraction and increased the frequency of spontaneous action potentials recorded with micro-electrodes from bladder strips. Vasoactive intestinal peptide (VIP) produced relaxation and slowed action potentials in rabbit but had no effect in guinea-pig; neurotensin, somatostatin and leu-enkephalin were without action in either species. When the tissue was kept in contact with SP, a second application after 10 min produced only a small contraction suggesting that SP receptors were desensitized. However, the electrical response to field stimulation was unchanged and the mechanical response was increased. Chymotrypsin reduced mechanical responses to SP but had no effect on responses to field stimulation. The SP analogue, D-Pro2, D-Phe7, D-Trp9-SP, had no effect on responses to SP or to field stimulation. It is concluded that the bladder receives excitatory non-cholinergic innervation which is responsible for a large excitatory junction potential and contraction. Although SP can contract the detrusor muscle, it is unlikely that it is an excitatory transmitter or that any of the five peptides act as modulators of transmitter release.
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PMID:Non-cholinergic neurotransmission and the effects of peptides on the urinary bladder of guinea-pigs and rabbits. 242

We have studied the selectivity and competitiveness of three neurokinin antagonists and atropine against substance P, neurokinin A, and neurokinin B. DPDTNLE-NB, [D-Pro2, D-Trp6,8, Nle10]-neurokinin B is a competitive antagonist of neurokinin B (pA2 = 5.5), but not substance P or neurokinin A. DPDT-SP ([D-Pro2,Trp7,9]-substance P), competitively blocks substance P (pA2 = 6.9) and neurokinin B (pA2 = 6.8), but not neurokinin A. Spantide ([D-Arg1, D-Trp7,9, Leu11]-substance P) competitively blocks substance P (pA2 = 6.7) and at a log unit higher concentration blocks neurokinin A (pA2 = 5.8), but does not block neurokinin B. Atropine is a competitive antagonist of neurokinin B (pA2 = 9.0) at ten times the concentration needed to block acetylcholine (pA2 = 10.1), but does not inhibit the other neurokinins. These results support the hypothesis of multiple neurokinin receptors in the guinea pig ileum and indicate that the site of neurokinin B, but not substance P or neurokinin A is predominantly on intramural neurons. This indirect stimulation appears to be dependent on the release of acetylcholine. Neurokinin B also has activity on smooth muscle receptors since the contractile response could not be completely antagonized by atropine. There appear to be two smooth muscle neurokinin receptors on the basis of results obtained with DPDT-SP and spantide, one predominantly responsive to substance P and the other to neurokinin A. Only spantide appeared to have any effect on the neurokinin A receptor and that was at a much higher concentration than that needed to block substance P.
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PMID:Differentiation of multiple neurokinin receptors in the guinea pig ileum. 243 Dec 45

The gastric motor or mechanical effects of a group of peptides, the tachykinins, were evaluated in anesthetized cats to determine the relationship between local motor events and brain stem neurons that regulate gastric activity. The peptides evaluated were substance P, physalaemin, and eledoisin. The tachykinin-induced gastric changes were dose related and were characterized by initial distention-sustained contraction-late distention phases. At lower doses distention was the dominant effect with a sustained contraction-late distention response appearing as the dose increased. The sustained contraction-late distention phases were frequently accompanied by phasic contractions with a frequency of 2-4/min. Atropine had a significant effect on the sustained contraction phase but no effect on the phasic contractions or distention phases. Bilateral cervical vagotomy had a significant effect on the early distention phase, suggesting a link with brain stem mechanisms. The activity of brain stem units that responded to phasic distention of the stomach reflected the tachykinin-induced changes in gastric distention. Although the gastric effects of these tachykinins shared distinct similarities, certain differences in the time sequence of the distention-contraction interactions suggests the possibility that dissimilar receptor types may be involved in the mechanisms of action. Their mechanisms of action may also involve a direct effect on the effector organ.
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PMID:Tachykinins: local gastric effects and brain stem responses. 243 67

Experiments were performed on cats anesthetized with thiopental sodium and gallamine triethiodide and ventilated artificially. Gastric motility was recorded by a balloon method. Electrical stimulation of the vagal trunk in cats with chronic supranodose vagotomy for 11 to 32 days caused an excitatory response of the stomach. The pulse duration of electrical stimulation to obtain a maximal excitatory response of the stomach was 3 msec. Administration of hexamethonium (10 mg/kg i.v.) did not inhibit but enhanced the excitatory response of stomach. Atropine (3, 10 and 30 micrograms/kg i.v.), hemicholinium (10 mg/kg i.v.) and morphine (5 mg/kg i.v.) inhibited this hexamethonium-resistant excitatory response of the stomach, whereas treatment with physostigmine (300 mu/kg i.v.) augmented it. A substance P antagonist, (D-Pro2, D-Trp7.9)-substance P (250 and 500 micrograms/kg i.v.), did not affect the hexamethonium-resistant excitatory response. Acetylcholine content of the nodose ganglion 6 to 8 days after supranodose vagotomy was assayed using the radioenzymatic method, and the level was about 48% that of the intact ganglion. These results suggest that the gastric excitatory response to stimulation of the supranodose denervated vagal trunk is produced by activation of vagal afferent fibers probably originating from the nodose ganglion; the fibers involved are cholinergic.
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PMID:Gastric excitation by stimulation of the vagal trunk after chronic supranodose vagotomy in cats. 243 91

The effect of parasympathetic nerve activation on rabbit submandibular gland (SMG) blood flow and saliva secretion were studied before and after systemic administration of atropine or hexamethonium. The parasympathetic fibers were stimulated electrically (2 and 15 Hz, 10 V, 1 msec) at the plexus around the submandibular salivary duct or at the chorda lingual nerve. In untreated animals, stimulation of parasympathetic fibers caused a frequency-dependent increase of salivary secretion and blood flow in the SMG. Atropine treatment completely abolished saliva secretion at 2 Hz and 15 Hz and the increase in SMG blood flow during stimulation at 2 Hz. Although atropine significantly reduced the vasodilatory response at 15 Hz, the highest blood flow measured under such circumstances was still about 2.5 times the prestimulation value. After hexamethonium administration no blood flow increase or saliva secretion was seen upon chorda lingual stimulation. The concentration of vasoactive intestinal polypeptide (VIP)-like immunoreactivity in the venous effluent of the SMG increased during nerve stimulation. Atropine significantly reduced, and hexamethonium abolished this VIP-output elicited by parasympathetic nerve stimulation. Local infusion of VIP, peptide histidine isoleucine (PHI) and substance P all caused atropine-resistant vasodilation but no salivation. The present data suggest that VIP and possibly PHI play a role in the atropine-resistant vasodilatation in rabbit submandibular gland elicited by parasympathetic nerve stimulation. The contribution of sensory mediators such as substance P released by stimulation of afferent nerves in the chorda lingual nerve to the salivary and vasodilatory responses seems to be of minor importance in the rabbit submandibular gland.
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PMID:VIP and noncholinergic vasodilatation in rabbit submandibular gland. 243 46

To elucidate how substance P (SP) produces submucosal gland secretion, we examined the effects of SP on the glandular contractile response and 3H-labeled glycoconjugate release in isolated submucosal glands from feline tracheae. SP (10(-12) to 10(-4) M) produced dose-dependent increases in the contractile response, and the maximal tension induced by SP was approximately 70% of the response to methacholine. SP-induced contraction is blocked completely by atropine and augmented by neostigmine. Pretreatment with hemicholinium 3, an acetylcholine synthesis inhibitor, inhibited the contractile response to SP. Pretreatment with tetrodotoxin did not inhibit the contractile response to SP. Capsaicin induced tension of a magnitude similar to that of SP. SP (10(-7) M) produced a significant increase (74% above control) in radiolabeled glycoconjugate release from isolated glands, whereas SP had no significant effects on glycoconjugate release from tracheal explants, probably because of epithelial suppression. Atropine abolished SP-evoked glycoconjugate release in isolated glands. Our findings indicate that 1) SP induces glandular contraction, which is related to the squeezing of mucus in the ducts and secretory tubules, 2) SP stimulates radiolabeled glycoconjugate release in isolated submucosal gland, probably involving mucus synthesis and/or cellular secretion, and 3) these two actions are mediated by a peripheral cholinergic mechanism.
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PMID:Effect of substance P on mucus secretion of isolated submucosal gland from feline trachea. 244 76

To determine the role of endogenous enkephalinase (EC 3.4.24.11) in regulating peptide-induced contraction of airway smooth muscle, we studied the effect of the enkephalinase inhibitor, leucine-thiorphan (Leu-thiorphan), on responses of isolated ferret tracheal smooth muscle segments to substance P (SP) and to electrical field stimulation (EFS). Leu-thiorphan shifted the dose-response curve to SP to lower concentrations. Atropine or the SP antagonist [D-Pro2,D-Trp7,9]SP significantly inhibited SP-induced contractions in the presence of Leu-thiorphan. Leu-thiorphan increased the contractile responses to EFS dose dependently, an effect that was significantly inhibited by the SP antagonist [D-Pro2,D-Trp7,9]SP. SP, in a concentration that did not cause contraction, increased the contractile responses to EFS. This effect was augmented by Leu-thiorphan dose dependently and was not inhibited by hexamethonium or by phentolamine but was inhibited by atropine. Because contractile responses to acetylcholine were not significantly affected by SP or by Leu-thiorphan, the potentiating effects of SP were probably on presynaptic-postganglionic cholinergic neurotransmission. Captopril, bestatin, or leupeptin did not augment contractions, suggesting that enkephalinase was responsible for the effects. These results suggest that endogenous tachykinins modulate smooth muscle contraction and endogenous enkephalinase modulates contractions produced by endogenous or exogenous tachykinins and tachykinin-induced facilitation of cholinergic neurotransmission.
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PMID:Enkephalinase inhibitor potentiates substance P- and electrically induced contraction in ferret trachea. 244 55

To determine the roles of endogenous enkephalinase (EC.3.4.24.11) in regulating tachykinin-induced contraction of airway smooth muscle, the authors studied the effects of the enkephalinase inhibitor leucine-thiorphan on the contractile responses to substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) in isolated ferret tracheal smooth muscle segments. Leucine-thiorphan shifted, in concentration-dependent fashions, the dose-response curves to all tachykinins to lower concentrations. Leucine-thiorphan changed the rank order of tachykinin potency from NKA greater than SP greater than NKB to NKA = NKB greater than SP. Removal of the epithelium slightly enhanced the contractile responses to SP and NKA but not to NKB. Atropine shifted the dose-response curves of all tachykinins to higher concentrations. Each tachykinin increased the contractile response to electrical field stimulation (5 Hz, 20 sec of duration, 20 V) in a dose-dependent fashion. This effect was not altered by hexamethonium, indomethacin, BW755C or naloxone but was potentiated by leucine-thiorphan and inhibited by the tachykinin receptor antagonist (D-Pro2, D-Trp7,9)-SP and by atropine. Because tachykinins did not affect contractile responses to acetylcholine significantly, their effects were probably on presynaptic postganglionic nerves. Captopril, bestatin and leupeptin did not alter contractile responses, suggesting that angiotensin converting enzyme, aminopeptidases and serine proteinases did not modulate tachykinin-induced effects. Enkephalinase immunofluorescence was found in the smooth muscle and epithelium and confirmed the authors' finding of enkephalinase-like activity in the muscle. The results suggest that tracheal enkephalinase is an important modulator of tachykinin-induced effects.
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PMID:Enkephalinase inhibitor potentiates mammalian tachykinin-induced contraction in ferret trachea. 244 68

1. The onset and development of functional innervation of intramural neurones were examined by transmural nerve stimulation in circular muscle strips isolated from the rat stomach during the period from embryonic day (ED) 15 to 7-days postnatal. 2. At ED 15, transmural stimulation elicited an atropine-sensitive contraction in about half of the preparations. From ED 16, it caused a frequency-dependent contraction in all preparations. Physostigmine significantly potentiated the amplitude of the nerve-mediated contraction until ED 18. 3. Atropine inhibited but failed to abolish the contractile response to nerve stimulation in all preparations from ED 16. 4. During the contraction induced by carbamylcholine (CCh), transmural stimulation caused a biphasic response consisting of a contraction followed by a relaxation at ED 18 and ED 19, but caused a triphasic response consisting of a rapid relaxation followed by the biphasic response after birth. 5. CCh and substance P (SP) elicited contractions at ED 15 and vasoactive intestinal polypeptide (VIP) caused a relaxation at ED 16. The sensitivity to CCh and VIP increased with development but that to SP did not change. 6. The results suggest that functional intramural cholinergic and non-cholinergic excitatory innervations in the rat stomach are established almost simultaneously by ED 16, and the onset of functional intramural non-adrenergic inhibitory innervation lags about 2 days behind that of functional excitatory innervations.
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PMID:Development of non-cholinergic, non-adrenergic excitatory and inhibitory responses to intramural nerve stimulation in rat stomach. 245 45

The role of rat calcitonin gene-related peptide (CGRP), a recently characterized vasoactive neuropeptide, in cardiovascular regulation was studied in the conscious rat. Mean arterial pressure (MAP), heart rate, cardiac output (thermodilution technique) and regional blood flow (directional pulsed Doppler velocimetry) were monitored after i.v. or i.c.v. administration of CGRP. Systemic administration of CGRP (0.1-10 nmol/kg i.v.) decreased MAP and increased heart rate in a dose-related manner. Cardiac output increased (+95 +/- 16 ml/min/kg, P less than .01) after the 1-nmol/kg dose. At the lower or higher doses, CGRP produced no consistent changes in cardiac output. Total peripheral resistance was decreased significantly at the doses of 1 and 10 nmol/kg of CGRP. The CGRP i.v. doses of 1 and 10 nmol/kg increased mesenteric and hindquarter blood flow to a maximum of +23 +/- 7 and +30 +/- 6%, respectively (P less than .01). An increase in renal blood flow (+19 +/- 6%, P less than .05) and a decrease in renal resistance (-15 +/- 4%, P less than .05) were produced by the 0.1-nmol/kg dose of CGRP which had no effect on MAP; higher doses of CGRP tended to decrease renal blood flow. The resistance in all vascular beds was decreased by the CGRP doses of 1 and 10 nmol/kg. The maximum decreases in mesenteric, renal and hindquarter vascular resistance after the 10-nmol/kg dose were -53 +/- 3, -42 +/- 5 and -48 +/- 4%, respectively (P less than .01). The hypotensive and vasodilator responses to CGRP i.v. were significantly magnified, and the tachycardia produced by CGRP was attenuated in the sinoaortic denervated rats. Atropine (muscarinic blockers), propranolol (beta adrenoceptor blocker), cimetidine and pyrilamine (histamine H1 and H2 blockers), indomethacin (prostaglandin synthesis inhibitor), BN52021 (platelet activating factor antagonist) or a substance P antagonist had no effect on the cardiovascular responses elicited by systemic CGRP. CGRP, i.c.v. (0.1-10 nmol/kg), induced a modest tachycardia in both intact and sinoaortic denervated rats, but was devoid of any other cardiovascular effects. The results indicate that CGRP is a potent vasodilator of mesenteric, renal and hindquarter skeletal muscle blood vessels in the conscious rat. The hypotensive and vasodilator actions of circulating CGRP are likely to be mediated by direct peripheral interaction with CGRP receptors on vascular smooth muscle, whereas its tachycardic effect seems to involve reflex activation of the sympathetic nervous system.
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PMID:Cardiovascular effects of rat calcitonin gene-related peptide in the conscious rat. 245 71

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