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)

Neonatal mice, under fasting conditions, are susceptible to the development of lesions in the arcuate nucleus (AN) of the hypothalamus, with high doses of monosodium L-glutamate (MSG). Feeding of nutrients (e.g., sugars and L-amino acids) has been shown to have a protective effect against the development of these lesions. The purpose of these studies was to elucidate the mechanism of this protective effect. Histopathologic examination of lesions of the AN demonstrated that feeding of weaning mice before subcutaneous administration of toxic doses of MSG suppressed the development of these lesions, as compared to fasted controls. Similarly, the number of necrotic cells in the AN of neonates administered toxic doses of MSG subcutaneously was reduced when D-glucose and L-arginine were administered orally. Atropine obliterated the protective effect of D-glucose. Pretreatments consisting of gastric inhibitory polypeptide (GIP) + oral D-glucose had a protective effect of higher potency than GIP alone. Pretreatments with insulin, anorexigenic peptide (pyroGlu-His-Gly), cholecystokinin, glucagon, bombesin, and substance P (in decreasing order of effectiveness) demonstrated a protective effect against the AN lesion in neonates, whereas somatostatin and beta-endorphin had no effect. Results suggest that the protective effect of nutrients may in part be due to the stimulation of peptide hormone release during the postabsorptive phase. It is postulated that the effect of entero-pancreatic hormone, especially insulin, is to enhance the tolerance of AN neurons of neonatal mice to the toxic dose of L-glutamate.
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PMID:Mealing and related hormone release suppress hypothalamic lesions of neonatal mice by L-glutamate. 288 96

By immunohistochemistry, nerve fibers containing gastrin-releasing polypeptide (GRP)-like immunoreactivity were identified close to the somatostatin (SS)-producing cells of the gastric antral mucosa. We, therefore, studied the possible role of GRP in the control of antral SS secretion by use of isolated perfused pig antrum with intact vagus nerve supply. Electrical stimulation of the vagus nerves at 4 Hz increased the antral release of GRP up to 10-fold and increased SS output 2- to 3-fold. Atropine at 10(-6) M had no effect on these responses. Intra-arterial GRP increased SS secretion significantly at 10(-10) M and eightfold at 10(-8) M, whereas gastrin secretion was stimulated significantly at 10(-11) M and maximally at 10(-10) M and inhibited at 10(-8) M. Preperfusion with a GRP antagonist ([D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P) or Fab fragments of antibodies against GRP abolished the effects of vagus stimulation on gastrin and somatostatin output. Gastrin in concentrations up to 10(-7) M was without effect on SS secretion. We conclude that electrical stimulation of the vagus nerves increases antral SS gastrin secretion and that GRP is a likely transmitter.
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PMID:GRP-producing nerves control antral somatostatin and gastrin secretion in pigs. 289 16

1 The interaction between amphetamine and the alpha 2-adrenoreceptor agonists, clonidine and guanabenz, was studied in the submaxillary gland of anaesthetised rats. 2 Low doses of clonidine (10 micrograms/kg) and guanabenz (10 micrograms/kg) inhibited the secretory responses induced by methacholine and substance P, respectively. 3 Amphetamine (300 micrograms/kg) antagonized the inhibitory effects of both alpha 2-agonists. This dose of amphetamine alone did not show sialagogic effects. 4 Atropine (1 micrograms/kg) diminished the secretory responses to methacholine as much as clonidine (10 micrograms/kg). Amphetamine did not modify the blockade by atropine. 5 Guanabenz (10 micrograms/kg) markedly decreased the secretory responses to substance P, an effect that was also prevented by amphetamine. 6 Reserpine pretreatment (5 mg/kg, i.p., 18 h) did not alter the effect of amphetamine. 7 These results indicate that the interaction between amphetamine and alpha 2-adrenoreceptor agonists is unrelated to the indirect effect of this amine and suggest a direct interaction between the drug and postsynaptic inhibitory alpha 2-adrenoreceptors.
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PMID:Interaction between amphetamine and alpha 2-postsynaptic adrenoreceptors in the rat submaxillary gland. 289 39

Bacterial N-formyl-methionyl oligopeptides are spasmogenic for guinea-pig ileum in vitro but the mechanism of this effect is not understood. To investigate this phenomenon further, we have determined pA2 values (the negative logarithm of the concentration of an antagonist reducing a double-dose agonist response to a single-dose response) for a number of potential antagonists of N-formyl-met-leu-phe (F-met-leu-phe) using histamine, acetylcholine, 5HT and substance P as control agonists. Atropine, pirenzepine and tetrodotoxin were potent inhibitors of F-met-leu-phe induced contraction (pA2's 8.4, 8.0 and 7.9, respectively) suggesting involvement of neural and cholinergic pathways in the response. Sulphasalazine, known to block the F-met-leu-phe receptor on neutrophil leucocytes, was also a potent inhibitor. Tachyphylaxis induced by either 5HT, or substance P, did not diminish the response to F-met-leu-phe, suggesting that these potential mediators were not involved. These studies indicate that bacterially synthesized formyl-methionyl oligopeptides bind to cells bearing receptors in guinea-pig ileum and produce muscle contraction via enteric cholinergic (M1) neural pathways.
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PMID:Involvement of M1 cholinergic receptors and enteric nerves in the spasmogenic activity of bacterial N-formyl oligopeptides on guinea-pig ileum. 297 53

A study of the effects of substance K (SK) and its synthetic fragments on salivation was performed. The rank order of potency of tachykinins that elicited salivation was as follows: physalaemin greater than substance P greater than eledoisin greater than kassinin greater than Arg-SK-(1-10) greater than SK-(1-10) greater than SK-(3-10). SK-(6-10) showed no activity. Atropine (1 mg/kg i.v.) had no effect on SK-induced salivation.
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PMID:Effect of a novel tachykinin, substance K, on salivation in rats. 299 Sep 59

Atropine-resistant longitudinal contractions of the guinea-pig ileum due to field stimulation were greatly augmented by theophylline (150 microM). Adenosine exerted an opposite effect. Theophylline did not potentiate contractions evoked by exogenous substance P. It is suggested that a theophylline-sensitive inhibitory mechanism (possibly mediated by adenosine or a related substance) controls transmitter release from enteric non-cholinergic excitatory neurones.
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PMID:Theophylline-sensitive modulation of non-cholinergic excitatory neurotransmission in the guinea-pig ileum. 299 77

The characteristics of smooth muscle responses to transmural nerve stimulation in the rabbit iris sphincter were examined. Transmural stimulation elicited a composite contractile response that could be divided in two phases. Atropine abolished the phase I contraction and inhibited the phase II contraction. The atropine-resistant component of the phase II contraction which was unaltered by sympathetic denervation, was mimicked by substance P and abolished by capsaicin. Adenosine inhibited the phase I contraction. The adenosine analogue L-N6-phenylisopropyladenosine (L-PIA) was more potent than 5'-N-ethylcarboxamideadenosine (NECA) in mimicking this adenosine effect. By contrast, adenosine enhanced the phase II contraction in non-pretreated preparations, as well as the atropine-resistant capsaicin-sensitive part of this contraction. Here, NECA was more potent than L-PIA. Adenosine, NECA, L-PIA and D-PIA also enhanced the atropine-sensitive component of the phase II contraction, as well as the contractile response to exogenous acetylcholine or carbachol, but not to exogenous substance P. In this respect, L-PIA was the most powerful adenosine analogue with at least 10 fold higher potency than D-PIA. The adenosine antagonist 8-p-sulphophenyltheophylline enhanced the phase I contraction and decreased the capsaicin-sensitive non-adrenergic non-cholinergic component of the phase II contraction. We conclude that adenosine inhibited the nerve-induced cholinergic twitch (phase I) responses by action at prejunctional A1-receptors. Furthermore, adenosine enhanced the phase II contractile responses via postjunctional enhancement of the cholinergic transmission by action at A1-receptors, and via enhancement of the non-adrenergic non-cholinergic transmission by action at presumably prejunctional A2 receptors.
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PMID:Adenosine-modulation of cholinergic and non-adrenergic non-cholinergic neurotransmission in the rabbit iris sphincter. 301 Nov 72

Isolated segments of rat and guinea pig midcolon were used to examine the neurotransmitters responsible for ascending contraction and descending relaxation components of the peristaltic reflex. Graded radial stretch of the extreme orad end caused only descending relaxation accompanied by significant release of vasoactive intestinal peptide (VIP) in rat (82%, P less than 0.005) and guinea pig (47%, P less than 0.05). Radial stretch of the caudad end caused only ascending contraction without VIP release. VIP antiserum (1:480 to 1:60) inhibited descending relaxation in a concentration-dependent manner at all grades of stretch (40 +/- 12% to 74 +/- 15%) but augmented ascending contraction (25 +/- 7% to 108 +/- 21%). Axonal blockade with tetrodotoxin and ganglionic blockade with hexamethonium abolished both components, indicating the participation of cholinergic neurons. Atropine and the tachykinin antagonist [D-Pro2,D-Trp7,9]substance P inhibited ascending contraction but not descending relaxation; their combination abolished ascending contraction at all grades of stretch. We conclude that cholinergic neurons coupled to VIP motor neurons regulate descending relaxation and that cholinergic neurons coupled to tachykinin and cholinergic motor neurons regulate ascending contraction.
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PMID:Colonic peristaltic reflex: identification of vasoactive intestinal peptide as mediator of descending relaxation. 301 95

Motilin has a stimulating effect on gastrointestinal motility. The mechanism of its action is not known. Direct and neuronal effects have been postulated. To determine if receptors are present on smooth muscle cells we investigated the effect of synthetic porcine motilin and its interaction with acetylcholine on isolated guinea pig gastric smooth muscle cells. Motilin elicited a dose-dependent contraction of gastric smooth muscle cells. Minimal (8.3 +/- 1.3%) and maximal (33.9 +/- 2.4%) responses were observed at 10(-12) and 10(-6) M, respectively. The ED50 of motilin was 10(-9) M. Acetylcholine also elicited a dose-response muscle contraction with a maximal response observed at 10(-7) M. Atropine (10(-7) M) completely inhibited the maximal response to acetylcholine but did not have any effect on the contractile response to motilin. In addition, dibutyryl guanosine 3',5'-cyclic monophosphate (10(-3) M) and substance P antagonist, spantide (10(-4) M), also did not inhibit the action of motilin. Acetylcholine (10(-11) M) shifted the dose-response curve of motilin to the left by 1.5 log units. The maximal response to the combination of motilin (10(-6) M) and acetylcholine (10(-11) M) was 32 +/- 3.2%, which was similar to the maximal response to motilin alone. It is concluded that distinct motilin and muscarinic receptors are present on guinea pig gastric smooth muscle cells. The interaction between motilin and acetylcholine is additive and not potentiative.
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PMID:Motilin receptors on isolated gastric smooth muscle cells. 334 75

The neuropeptide substance P (SP) released from airway sensory C fibers accelerates mucociliary activity, and C fibers in the airways are stimulated by various irritants including ammonia (NH3) vapor. The short-term effects of NH3 vapor on mucociliary function in the in the maxillary sinus of rabbits anesthetized with urethane were investigated by a photoelectric technique. Challenges with 1.5 ml NH3 increased mucociliary activity dose-dependently, the maximal response being 26.6 +/- 1.6%. The increase appeared within 1.3 +/- 0.3 s after exposure. Atropine and hexamethonium decreased the effect of NH3, indicating that part of the response was mediated by cholinergic effector neurons, but a noncholinergic effect clearly remained. Pretreatment with large doses of capsaicin (13 mg i.a.) abolished the response, whereas the SP antagonist (D-Pro2, D-Trp7,9) SP inhibited the noncholinergic response. Challenges with NH3 vapor also decreased the respiratory rate. An identical response was noticed during injections with the C fiber stimulant capsaicin. Together these results indicate that NH3 vapor triggers a mucociliary protective reflex in the airways, involving capsaicin-sensitive C fibers. The recorded increase of mucociliary activity is probably due to the combined effect on the mucociliary system of both SP and acetylcholine released from the afferent and efferent part of the reflex arc, respectively.
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PMID:Stimulation of C fibers by ammonia vapor triggers mucociliary defense reflex. 357 9


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