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)

Salivary flow and amylase secretion induced by substance P(SP) administered intraventricularly were considerably less than that by SP given intravenously (i.v.). Salivary flow induced by SP (i.v.) was partially inhibited by baclofen, atropine, d-tubocurarine, alcuronium, phenylephrine and PGE2, while it was enhanced by arachidonic acid and indomethacin. Salivary amylase secretion induced by SP given i.v. was enhanced markedly by isoproterenol, phenoxybenzamine, phentolamine and No. 865-123 (an adrenergic neuron blocking agent), and moderately by baclofen, PGE2 and arachidonic acid, while it was not influenced by propranolol. The enhancements of amylase secretion by adrenergic alpha-blockers were completely inhibited by propranolol. The in vitro examination using rat brain synaptosomes showed that SP promoted markedly the synthesis of PGs, especially of PGE2. These results suggest that the SP-receptor has a nicotinic receptor-like property and may be closely related to adrenergic alpha-receptors situated postsynaptically and presynaptically and to postsynaptic PGE2-receptors. From these results, it is concluded that SP-induced salivary flow and amylase secretion are modulated by the promotion of PGs synthesis in the autonomic nervous system.
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PMID:[Mechanism of substance P-induced salivary secretion in the rat: effect of substance P on autonomic nervous system and prostaglandin synthesis (author's transl)]. 615 81

In dispersed acinar cells from the guinea pig pancreas, substance P (SP) was found to stimulate outflux of 45Ca, cellular accumulation of cyclic GMP, and release of amylase. Maximal effects on accumulation of cyclic GMP and release of amylase were obtained with 3 x 10(-8) M of SP, 10(-7) M of Sp caused maximal outflux of 45Ca. These effects corresponded to 30-50% of the maximal effects obtained with caerulein, a cholecystokinin-like decapeptide. The concentrations of SP required for stimulation of 45Ca outflux, accumulation of cyclic GMP, and release of amylase correspond well with those which affect binding of 125I-tyr8-SP to pancreatic acinar cells.
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PMID:Interaction of substance P with dispersed pancreatic acinar cells from the guinea pig. Stimulation of calcium outflux, accumulation of cyclic GMP and amylase release. 616 Jul 30

1 The effects of substance P and related peptides on amylase release from rat parotid gland slices have been investigated. 2 Supramaximal concentrations (1 microM) of substance P caused enhancement of amylase release over the basal level within 1 min; this lasted for at least 40 min at 30 degrees C. 3 Substance P-stimulated amylase release was partially dependent on extracellular calcium and could be inhibited by 50% upon removal of extracellular calcium. 4 Substance P stimulated amylase release in a dose-dependent manner with an ED50 of 18 nM. 5 All C-terminal fragments of substance P were less potent than substance P in stimulating amylase release. The C-terminal hexapeptide of substance P was the minimum structure for potent activity in this system, having 1/3 to 1/8 the potency of substance P. There was a dramatic drop in potency for the C-terminal pentapeptide of substance P or substance P free acid. Physalaemin was more potent than substance P (ED50 = 7 nM), eledoisin was about equipotent with substance P (ED50 = 17 nM), and kassinin less potent that substance P (ED50 = 150 nM). 6 The structure-activity profile observed is very similar to that for stimulation of salivation in vivo, indicating that the same receptors are involved in mediating these responses. 7 All the fragments of substance P tested were capable of eliciting a full amylase release response. This indicates that the apparent partial agonist action of the C-terminal nonapeptide fragment on in vivo salivation is not explicable at the receptor level.
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PMID:The effects of substance P and related peptides on alpha-amylase release from rat parotid gland slices. 616 21

A modified fluorescence assay for alpha-amylase activity is described. The method employs amylopectin anthranilate as substrate and offers the advantages of economy of time and resources over a previously described technique using the same substrate. The sample containing alpha-amylase is incubated with the substrate for 5 min at 30 degree C in a final volume of 750 microliter. The fluorescent products of the reaction are separated from the substrate by the addition of methanol, and the methanol-soluble fluorescence is measured in a fluorescence spectrometer. A highly reproducible linear relationship between fluorescence and alpha-amylase activity is obtained for enzyme activities up to 2 units. The absolute sensitivity of the assay under these conditions was estimated to be 0.02 EU (= 0.08 EU ml-1). The application of the assay method to a study of the effects of isoprenaline and substance P-like peptides on the release of alpha-amylase from rat parotid gland slices is described. The assay is particularly suitable for studies on agonists, such as substance P, which have a low ceiling effect in terms of amylase release.
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PMID:A modified amylase assay, using a fluorescent substrate, and its application to a study of the rat parotid gland in vitro. 617 29

With appropriate measures to protect 3H-substance P (3H-SP) from proteolytic degradation and from nonspecific adsorption to glass-fiber filters, we have been able to demonstrate reliably a high-affinity specific binding of 3H-SP to rat submaxillary/sublingual gland membranes with a KD of 1 nM and Bmax of 6 pmoles/g of tissue. The relative potencies of various SP fragments and related analogues in reducing 3H-SP binding parallel their potencies in stimulating phosphatidylinositol turnover, amylase release, and salivation, thus supporting an association of the observed 3H-SP binding site with the physiological SP receptors in this tissue. This binding is selectively stimulated by some divalent cations (Mn2+ greater than Mg2+ greater than Ca2+) but inhibited by several guanyl nucleotides, suggesting a possible linkage to adenylate cyclase. However, no effect of SP on either the basal or the norepinephrine-stimulated adenylate cyclase activity could be demonstrated in salivary gland homogenates.
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PMID:3h-substance P binding to salivary gland membranes. Regulation by guanyl nucleotides and divalent cations. 619 Nov 91

Secretion of fluid, ions, and amylase from parotid and submaxillary glands of rat, induced by intravenous injection of substance P (SP), was examined. The action of SP on salivary glands, like physalaemin, resembled that of cholinergic stimulation. While SP-evoked salivary flow from both glands was blocked by atropine, atropine did not modify composition of SP-evoked saliva. The present study suggests that salivary secretion and secretion of ions and amylase evoked by SP are mediated via SP-sensitive cholinergic receptors and specific SP receptors, respectively.
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PMID:Salivary secretion induced by substance P. 619 30

The relative potencies of a series of substance P analogues have been determined for spasmogenic activity in the guinea-pig ileum in vitro and for the release of 86Rb and alpha-amylase activity from rat parotid gland slices in vitro. Equipotent molar ratios (EMR), relative to substance P, were determined for all the compounds. In the rat parotid gland, EC50 values for amylase release were, on average, 35.5 times greater than those for 86Rb release. Analysis of Hill plots suggests that spare receptors exist for 86Rb release but not for amylase release and it is suggested that the stimulus-response coupling for amylase release may be less efficient than that for 86Rb release. In the parotid gland, the octapeptide and [less than Glu6]-hexapeptide C-terminal fragments of substance P were less active than substance P itself, whereas in the ileum, the octapeptide was as active as substance P. Substitutions at the Phe7 or Phe8 positions in general reduced activity relative to substance P. This effect was particularly apparent in C-terminal hexapeptide analogues. Substitutions at the Phe7 and Phe8 positions in C-terminal hexapeptide analogues produced a greater reduction in activity in the parotid gland than in the ileum. The most marked difference was observed with eledoisin-related peptide for which the ratio of EMRs for ileum and 86Rb release was 18.1. The unsubstituted C-terminal octapeptide fragment similarly showed a discrepancy between the two assay systems (EMR ratio, ileum: 86Rb release = 7.75). It is suggested that the results may indicate the presence of sub-populations of 'substance P receptors' which are represented at least in different proportions in the two tissues studied, although alternative explanations such as differences in metabolism of agonists are possible.
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PMID:Relative activities of substance P-related peptides in the guinea-pig ileum and rat parotid gland, in vitro. 619 40

The technique of electrical field stimulation was employed to stimulate the intrinsic nerves of isolated rat parotid gland fragments. Responses to field stimulation were recorded as changes in enzyme secretion (amylase release), radiolabelled ion fluxes (86Rb efflux) and electrophysiological effects (changes in acinar cell membrane potential and input resistance). All effects of field stimulation were abolished by the neurotoxin, tetrodotoxin (TTX). Selective use of pharmacological antagonists revealed that both the sympathetic and parasympathetic nerves to this tissue were being excited by field stimulation. Importantly a significant component of the response to field stimulation persisted in the presence of combined autonomic receptor blockade by atropine, phentolamine and propranolol, i.e. due to release of a non-cholinergic, non-adrenergic neurotransmitter. The non-cholinergic, non-adrenergic neurotransmitter evoked amylase release, 86Rb efflux and electrophysiological effects seen as changes in acinar cell membrane potential and conductance, i.e. stimulus-permeability coupled. Two biologically active peptides, substance P (SP) and vasoactive intestinal polypeptide (VIP) were shown to evoke amylase release in the presence of combined autonomic blockade. VIP however did not evoke any increase in 86Rb efflux, i.e. not stimulus-permeability coupled. All the effects of the non-cholinergic, non-adrenergic transmitter were mimicked by substance P which evokes 86Rb efflux and electrophysiological effects in addition to amylase release. The non-cholinergic, non-adrenergic field stimulus effects on amylase release and 86Rb efflux were abolished or markedly attenuated in tissues which had been desensitized by prior exposure to exogenous substance P. In the presence of VIP, however, the non-cholinergic, non-adrenergic effects persisted and were apparently potentiated. Acute application of the neurotoxin capsaicin first stimulated a transient release of amylase and subsequently abolished the non-cholinergic, non-adrenergic field stimulus-evoked enzyme release. The putative substance P antagonist, D-Pro2, D-Trp7,9 substance P, reversibly blocked the response to both non-cholinergic, non-adrenergic nerve stimulation and exogenous substance P. It was demonstrated however that prolonged exposure to this antagonist is associated with non-reversible and, importantly, non-specific neurotoxic effects. It is concluded that substance P or a closely related peptide is a functional neurotransmitter in the rat parotid gland.
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PMID:Substance P is a functional neurotransmitter in the rat parotid gland. 619 31

The effects of substance P on fluid and amylase secretion were examined in the exocrine pancreas of the rat and the mouse in vivo and in vitro. In the anaesthetised rat, a single intravenous injection of substance P caused an atropine resistant increase in both the basal and caerulein stimulated flow of pancreatic juice and amylase output, but reduced the secretin stimulated pancreatic juice flow. In vitro experiments using superfused mouse pancreatic fragments supported the in vivo result showing that substance P enhanced caerulein stimulated amylase output.
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PMID:Effects of substance P on fluid and amylase secretion in exocrine pancreas of rat and mouse. 620 66

In the present study we examined the abilities of three analogs of substance P, [D-Pro2-, D-Phe7-, D-Trp9]-substance P, [D-Pro2-, D- Trp7 ,9]-substance P and [D-Arg1-, D-Pro2-, D- Trp7 ,9-, Leu11 ]-substance P to alter substance P-induced changes in pancreatic acinar cell function and to occupy substance P receptors. At 30 microM, each analog of substance P lacked agonist activity and inhibited amylase secretion stimulated by substance P receptor agonists. The inhibition was reversible and specific for peptides that interact with substance P receptors (physalaemin, substance P, eledoisin, kassinin ). The analogs of substance P did not inhibit the actions of cholecystokinin, caerulein, gastrin, carbamylcholine, secretin, vasoactive intestinal peptide, PHI, ionophore A23187 or 8Br -cAMP. At high concentrations, [D-Arg1-, D-Pro2-, D- Trp7 ,9-, Leu11 ]-substance P, but not [D-Pro2-, D- Trp7 ,9]-substance P or [D-Pro2-, D-Phe7-, D-Trp9]-substance P, caused a small but significant inhibition of bombesin-stimulated amylase release. For each analog of substance P, the inhibition was competitive in nature in that there was a rightward shift of the dose-response curve for physalaemin-stimulated amylase secretion with no change in efficacy. From Schild plots of the ability of [D-Arg1-, D-Pro2-, D- Trp7 ,9-, Leu11 ]-substance P to inhibit either substance p- or physalaemin-stimulated amylase release, the slopes were not different from unity. For each analog of substance P, there was a close correlation between its ability to inhibit substance P- or physalaemin-stimulated amylase release and its ability to inhibit binding of 125I-labeled substance P or 125I-labeled physalaemin. [D-Arg1-, D-Pro2-, D- Trp7 ,9-, Leu11 ]-substance P was 2-fold more potent than [D-Pro2-, D- Trp7 ,9]-substance P which was 4-fold more potent than [D-Pro2-, D-Phe7-, D-Trp9]-substance P, (i.e., pA2 6.1, 5.9, and 5.2, respectively). For each analog, the dose-response curve for its ability to inhibit physalaemin-stimulated amylase release was superimpossible on the dose-response curve for its ability to inhibit binding of 125I-labeled physalaemin. These results indicate that each of these analogs of substance P is a specific competitive inhibitor of the action of the substance P on dispersed acini from guinea-pig pancreas, and that their abilities to inhibit substance P-induced changes in acinar cell function can be accounted for by their abilities to occupy the substance P receptor.
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PMID:Interaction of substance P antagonists with substance P receptors on dispersed pancreatic acini. 620 26


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