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)

Picomolar concentrations of neurotensin caused concentration-dependent contractions of the longitudinal musculature of the fundus of the rat stomach. The EC50 of neurotensin was approximately 1.5 nM. On a molar basis neurotensin was about 5-10 times more potent than 5-hydroxytryptamine (5-HT) and approximately 80 times as active as acetylcholine in producing similar contractions. Studies with structurally related peptides indicated that whereas the carboxy terminal portion of neurotensin was essential for biological activity, a substantial part of its amino terminus end could be removed without affecting its potency. The EC50 for the neurotensin fragment 8-13 was identical to that of neurotensin, however its 1-8 or 1-11 fragments were completely inactive. Tetrodotoxin did not modify the potency of neurotensin or structurally related analogues suggesting that the neurotensin receptor is probably located on the smooth muscle membrane. In addition, the potency of neurotensin in contracting the fundus was not modified by pretreatment with atropine, methysergide or diphenhydramine. Fade to the contractile response of neurotensin was followed by the development of tachyphylaxis; desensitization was concentration-dependent and characterized by a shift in the agonist concentration-response curve to the right and downwards. Desensitization with a priming concentration of neurotensin (approx. EC50) caused a substantial blockade of its excitability. There was cross-desensitization between neurotensin and the contractile activity of neurotensin 8-13 or xenopsin, but not with angiotensin II, bradykinin, substance P, acetylcholine, 5-HT or histamine. Pretreatment of the fundus strip with verapamil 0.3-1 microM antagonized in a concentration-dependent fashion the neurotensin-induced contractions but not the muscular contractions caused by acetylcholine. It is concluded that neurotensin activates a specific excitatory receptor probably located on the cell membrane of the smooth muscles of the rat fundus. In addition, we suggest that this receptor is somehow related to a voltage-dependent calcium channel, sensitive to verapamil.
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PMID:Excitatory neurotensin receptors on the smooth muscle of the rat fundus: possible implications in gastric motility. 298 83

Specimens from aganglionic (constricted) and ganglionic (dilated) gut were obtained from nine patients with Hirschsprung's disease. Transmural nerve stimulation of ganglionic smooth muscle in vitro evoked an initial relaxation followed by a contraction. This contraction was reduced but not abolished by atropine and it was further reduced by substance P antagonists. Guanethidine did not affect the electrically evoked responses. In aganglionic smooth muscle, an atropine-sensitive contraction but no initial relaxation was registered. Tetrodotoxin abolished all responses to electrical stimulation in both ganglionic and aganglionic specimens. Application of carbachol or substance P produced contraction and the adrenergic agonist isoprenaline or vasoactive intestinal peptide produced relaxation in ganglionic as well as aganglionic specimens. Two other gut neuropeptides, neuropeptide Y and galanin, were without effect. The results do not indicate a different receptor set up in ganglionic v aganglionic gut. The results are compatible with a lack of noncholinergic nonadrenergic inhibitory neurons in the aganglionic gut.
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PMID:Hirschsprung's disease: a comparison of the nervous control of ganglionic and aganglionic smooth muscle in vitro. 358 66

Studies were made on the mode of action of cholecystokinin octapeptide (CCK8) on longitudinal muscle strips of guinea pig ileum in vitro. CCK8 produced dose-related contractions of innervated strips of ileum longitudinal muscle (EC50 3--4 x 10(-9) M), but was inactive on denervated strips. Tetrodotoxin, and reducing the bath temperature to 15 degree C, abolished the response of innervated strips to CCK8. These results indicate that the action of CCK8 on ileal longitudinal muscle is mediated by the myenteric plexus. Atropine abolished the responses to acetylcholine and to low doses of CCK8. However, the responses to CCK8 in doses above 10(-8) M were reduced by atropine but not abolished. Incubation of longitudinal muscle strips with high concentrations of substance P (1.5 x 10(-7) M) resulted in desensitization to this peptide; this treatment inhibited the responses to CCK8 alone, and abolished the atropine-resistant actions of CCK8. Desensitization to substance P had no effect on the responses to acetylcholine, histamine, serotonin and angiotensin II. The results indicate that CCK8 contracts the longitudinal muscle of guinea pig ileum by releasing acetylcholine and substance P from the myenteric plexus.
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PMID:Evidence that the action of cholecystokinin octapeptide on the guinea pig ileum longitudinal muscle is mediated in part by substance P release from the myenteric plexus. 616 53

Effects of substance P on the isolated iris sphincter muscle of the albino rabbit were studied. The muscle was incubated in an organ bath containing Krebs' physiologic solution and the muscle tension was recorded with an isometric transducer. Substance P induced dose-dependent muscle contraction in the concentration range from 3 x 10(-11) to 3 x 10(-7) M and ED50 was estimated to be 3.7 x 10(-9) M. The muscle contraction was not antagonized by tropicamide, phentolamine, propranolol, chlorpheniramine, cimetidine, methysergide or baclofen. Tetrodotoxin (3 x 10(-7) g/ml) pretreatment did not change the muscle contraction induced by substance P. A retrobulbar capsaicin injection did not cause supersensitivity in the muscle response to substance P. These results indicate that the iris sphincter muscle contraction caused by substance P is not mediated by cholinergic-, adrenergic-, histamine- or serotonine-recepters and suggests that its action on the muscle is direct.
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PMID:Effects of substance P on the isolated iris sphincter muscle of the albino rabbit. 618 Jan 99

Substance P (SP) caused an immediate and vigorous contraction of the longitudinal smooth muscle layer of the guinea-pig ileum. The contractile response to SP, unlike that to acetylcholine or histamine was not maintained but faded to baseline levels in about 6 min. When 0.3-1.0 nM SP was added the fading time was shorter than 6 min and tachyphylaxis did not develop. Higher concentrations of SP produced fading times of about 6 min that could not be increased even by adding extremely high concentrations of the peptide, up to 1800 nM. Short fading times and the lack of development of tachyphylaxis are the result of the rapid adsorption and/or metabolism of SP. The addition of exogenous peptidases such as pronase, chymotrypsin and an extract of black widow spider venom gland dramatically increased the rate of degradation of SP, shortened the fading response and blocked the development of tachyphylaxis. Tetrodotoxin and atropine reduced the fading time by 25%, while eserine increased its duration several-fold; these findings are consistent with the existence of a cholinergic nerve component in the mediation of some of the effects of SP receptor and, in part, to adsorption and metabolism of the peptide. The magnitude of the tachyphylaxis to SP was proportional to the concentration of the desensitizing dose of the peptide and was specific to SP and to the related peptide physalaemin; no cross-tachyphylaxis towards other agents was found.
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PMID:Fading and tachyphylaxis to the contractile effects of substance P in the guinea-pig ileum. 618 Sep 10

Action potentials were recorded simultaneously from the longitudinal and circular muscle layers of the guinea pig isolated small intestine. Both the graded reflex of the longitudinal muscle and the peristaltic reflex proper could be evoked by raising the intraluminal pressure. At low intraluminal pressures, intervals between spike bursts of the circular muscle were longer than those of the longitudinal muscle. The higher the intraluminal pressure, the shorter became the intervals between spike bursts in the circular muscle, until both muscle layers showed synchronous discharge of action potentials. Tetrodotoxin (100 nM) abolished the excitation of both circular and longitudinal muscles produced by raising intraluminal pressure. Hexamethonium (280 microM) abolished excitation of the circular muscle but not that of the longitudinal muscle. Atropine (100 nM) reduced the excitatory effects of raising pressure on both muscle layers but did not abolish them. The atropine-resistant excitation of the circular, but not the longitudinal, muscle was reversibly blocked by exposure to substance P (100-500 nM). Chymotrypsin (200 micrograms/ml) reversibly abolished the atropine-resistant excitation of the circular muscle. It was concluded that during peristalsis both longitudinal and circular muscle layers are activated synchronously; muscle activation during peristalsis is not entirely cholinergic but may involve in addition a substance P-like peptide.
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PMID:Electrical activity of longitudinal and circular muscle during peristalsis. 618 7

Muscle strips were excised from the circular and longitudinal layers of the fundus, corpus and antrum of canine stomach, and from the inner portion of the pyloric ring (inner pylorus). Substance P (SP) induced strong contractions, with the greatest sensitivity in fundus and circular corpus preparations (threshold near 10 -10 mol/l). The sensitivity to SP decreased in the sequence circular corpus - longitudinal antrum - circular antrum (threshold near 10(-7) mol/l); it re-increased towards the pylorus, and in the inner pylorus was nearly as high as in the fundus. The SP responses of fundus and longitudinal corpus were purely tonic, similar to acetylcholine (ACh) and histamine (H) responses. In circular corpus, SP induced a combined phasic-tonic response. SP induced in antrum strips purely phasic-rhythmical contractions of low frequency (similar to the H response), whereas ACh induced phasic contractions of high frequency, and in addition an increase of tone in the longitudinal antrum strips. The SP responses of the inner pylorus were not uniform; in some preparations purely tonic contractions were observed, and large phasic fluctuations of low frequency occurred in others. The phasic components of all the responses were completely suppressed by nifedipine (10(-6) mol/l). Tetrodotoxin as well as blockade of adrenoceptors, of ACh and of H receptors had no effect on the SP responses. Comparative studies with preparations from guinea-pig showed that species differences exist in the SP responses of gastric muscle.
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PMID:Differentiated contractile responses of gastric smooth muscle to substance P. 619 Dec 75

Dissociated dopamine (DA) neurons from 14-day fetal mice were dissected from the rostral mesencephalic tegmentum (RMT) and were allowed to reaggregate in vitro with cells from the corpus striatum (CS). As previously demonstrated under these conditions, DA neurons develop punctate fluorescent varicosities and the capacity to synthesize, accumulate, and retain DA (Kotake, C., P. C. Hoffmann, and A. Heller (1982) J. Neurosci. 2: 1307-1315). After 17 to 22 days in culture, the RMT-CS coaggregates were assessed for their ability to release DA. Coaggregates were incubated in 5.6 x 10(-6) M [3H]DA, washed, and then superfused at 100 microliters/min for 2 hr. Fractions were collected every 2 min. Basal efflux of [3H]DA/2 min was 1% of tissue stores of 3H. K+, 70 mM infused for 8 min induced a peak release of 5.87% of tissue stores of 3H, and 50 mM K+ induced a peak release of 2.13%. The potassium-induced release of [3H]DA was calcium dependent. When d-amphetamine was infused for 12 min, 100 microM solutions induced a peak release of 8.91%, 10 microM induced a peak release of 4.36%, and 1 microM induced a peak release of 1.85% of tissue stores of 3H. Substance P at 100 microM induced a peak release of 2.19% of tissue stores of 3H. Tetrodotoxin (0.5 and 2.5 microM) decreased basal efflux by 40%, blocked substance P-induced release, but did not affect either potassium- or d-amphetamine-induced release of [3H]dopamine.
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PMID:Release of dopamine from coaggregate cultures of mesencephalic tegmentum and corpus striatum. 619 30

The mechanism underlying the positive inotropic and chronotropic effects of capsaicin were investigated using the spontaneously beating guinea-pig atrium in vitro. Capsaicin induced a long-lasting stimulatory effect (threshold dose 10(-9) M). Tetrodotoxin, phentolamine, 6-OHDA, mepyramine plus cimetidine, methysergide-, indomethacin-, somatostatin- or morphine pretreatment and local treatment with capsaicin on the vagal nerves did not reduce the capsaicin response, while it was abolished up to 1 month after systemic capsaicin pretreatment. The capsaicin response was subject to a rapid tachyphylaxis. During capsaicin tachyphylaxis, the positive inotropic and chronotropic effects of noradrenaline, serotonin and histamine were unchanged. Various neuropeptides were investigated with regard to cardiac activity. Physalaemin, eledoisin and somatostatin had negative inotropic and chronotropic effects. Substance P, bombesin, kassinin, CCK-8 or PHI (up to 10(-6)M of each) did not cause any detectable response on the guinea-pig auricle, while the substance P antagonist [D-Arg, D-Pro, D-Trp, Leu]SP induced a long-lasting stimulation of heart activity, VIP also stimulated the heart. Various adenyl compounds were also tested. Adenosine, AMP, ADP, ATP and beta-, gamma-methylene ATP had negative chronotropic and inotropic effects, while alpha-, beta-methylene ATP induced a stimulatory response. During alpha-, beta-methylene ATP tachyphylaxis, the auricles still responded to capsaicin. The inhibitory effects of adenosine and ATP analogues were antagonized by theophylline and 8-p-sulfophenyl theophylline. Capsaicin induced a small release of labelled nucleotides from 3(H)-adenine-prelabelled atria from control, but not from capsaicin-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Capsaicin-induced stimulation of the guinea-pig atrium. Involvement of a novel sensory transmitter or a direct action on myocytes? 620 51

The release of immunoreactive substance P (I-SP) from the myenteric plexus of the isolated guinea-pig small intestine and some of its characteristics have been investigated. Depolarizing stimuli, i.e. elevation of the extracellular K+ concentration or electrical field stimulation, increased the release of I-SP, the extent of the increase being dependent on the strength of the stimulus. Omission of Ca2+ from the bath medium prevented the stimulus-induced release of I-SP. Tetrodotoxin inhibited only the increase in I-SP release brought about by electrical stimulation but not that caused by elevated K+ concentrations. Gel exclusion chromatography on Sephadex G-25 showed that all the I-SP released by depolarization was co-eluted with authentic substance P. The methionine enkephalin analogue FK 33-824 significantly reduced the stimulus-induced release of I-SP, an effect that was prevented by the opiate antagonist naloxone. Naloxone alone significantly enhanced the stimulus-induced release of I-SP, which suggests that endogenously released opioid peptides also exert an inhibitory action on myenteric substance P-containing neurons. Putative excitatory neurotransmitters of the myenteric plexus, such as acetylcholine, bombesin, cholecystokinin octapeptide, and neurotensin, stimulated the release of I-SP in a tetrodotoxin-sensitive manner, whereas 5-hydroxytryptamine seemed ineffective. Capsaicin, known to release substance P from sensory neurons, also failed to alter the release of I-SP. The finding of a Ca2+-dependent release of I-SP caused by depolarizing stimuli further supports the concept that substance P is a neurotransmitter within the myenteric plexus. The activity of myenteric substance P-containing neurons appears to be controlled by a number of other putative enteric neurotransmitters.
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PMID:Characterization of the stimulus-induced release of immunoreactive substance P from the myenteric plexus of the guinea-pig small intestine. 620 63


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