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)

The effects of the neuropeptides VIP, PHM and substance P (SP) on vascular smooth muscle tone, K+ secretion from exocrine elements and tissue content of cyclic AMP (cAMP) in the human submandibular gland were studied in vitro. All three peptides caused relaxation of noradrenaline contracted human submandibular arteries at nM concentrations. SP was slightly more active than VIP and PHM which had a similar potency as vasodilators. Only carbachol but not VIP, PHM or SP stimulated K+ secretion from exocrine elements of the human submandibular gland. Principally similar in vitro effects on K+ secretion were obtained on the cat submandibular gland, but in the rat not only carbachol but also SP stimulated K+ secretion. VIP and PHM increased cAMP production of exocrine elements in the human submandibular gland in nM concentrations. VIP was about 5-fold more potent than PHM with regards to cAMP production. In conclusion, VIP, PHM and SP relaxed human submandibular arteries in vitro. Both VIP and PHM stimulated cAMP production in glandular tissue but none of the three peptides induced K+ secretion from human submandibular gland tissue. This suggests that, in contrast to the situation in the rat, SP does not cause watery salivation in man, while VIP and PHM may modulate protein e.g. amylase content of the saliva.
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PMID:Effects of VIP, PHM and substance P on blood vessels and secretory elements of the human submandibular gland. 242 7

Peptides which are possibly related to the non-cholinergic, non-adrenergic division of the autonomic nervous system have been identified by immunofluorescence in the digestive system of mature sheep. Vasoactive intestinal polypeptide-, substance P-, and bombesin-like immunoreactivity were localized in neural elements throughout the ovine gastrointestinal tract (g.i.t.). Vasoactive intestinal polypeptide-like immunoreactivity (VIP-l.i.) was demonstrable in the submaxillary, parotid and the sublingual salivary glands close to small blood vessels and the acini. VIP-l.i. was also demonstrable in the upper oesophagus in connective tissue near small blood vessels. In the forestomachs, abomasum, and small and large intestines reactive fibres were present in the mucosa, submucosa, smooth muscle layers and the plexuses. The plexuses also contained reactive nerve cell bodies. VIP-reactive fibres were found in the pancreas, the gall bladder and the common bile and pancreatic duct but were not found in the intestinal mesentery, portal vein, and liver tissue. Substance P-like immunoreactivity (SP-l.i.) was demonstrable in nerve fibres in all the layers of the g.i.t. and in nerve cell bodies in the gut plexuses. The pancreas and the gall bladder also contained a few scattered fibres. Additionally, SP-l.i. was present in open-type endocrine cells throughout the mucosa of the small and large intestines but no SP-l.i. was found in the salivary glands or the oesophagus. Bombesin-like immunoreactivity (B-l.i.) was associated with nerve fibres and was demonstrable in the mucosa and myenteric plexuses throughout the g.i.t. B-l.i. in the smooth muscle appeared to be restricted to nerve fibres in the forestomachs, the abomasum, and the upper small intestine. No B-l.i. was found in the salivary glands, oesophagus, liver tissue, pancreas, gall bladder or intestinal mesentery.
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PMID:The distribution of vasoactive intestinal polypeptide-like, substance P-like and bombesin-like immunoreactivity in the digestive system of the sheep. 243 32

Previous attempts to develop analogues of bombesin that function as specific receptor antagonists have been unsuccessful. Alteration of the histidine in luteinizing hormone releasing factor has resulted in analogues that function as competitive antagonists. In the present study we have used a similar strategy and altered the histidine in bombesin. [D-Phe12]bombesin, [D-Phe12,Leu14]bombesin, and [Tyr4,D-Phe12]bombesin did not stimulate amylase release from guinea pig pancreatic acini when present alone, but each analogue inhibited bombesin-stimulated secretion. For each analogue, detectable inhibition occurred at 1 microM and half-maximal inhibition at 4 microM. Each analogue inhibited amylase release by bombesin and other agonists that stimulate secretion by interacting with bombesin receptors. The analogues of bombesin did not alter stimulation by substance P or other agonists that interact with other receptors. The inhibition of the action of bombesin was competitive with Schild plots having slopes of 1.0. Each analogue also inhibited binding of 125I-labeled [Tyr4]bombesin but not 125I-labeled substance P. These results demonstrate that [D-Phe12] analogues of bombesin function as bombesin receptor antagonists and are the only bombesin receptor antagonists that interact only with the bombesin receptor. Because of their specificity, these analogues may prove useful for defining the role of bombesin in various physiological or pathological processes.
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PMID:[D-Phe12]bombesin analogues: a new class of bombesin receptor antagonists. 243 73

Intravenous injections of substance K (SK), a novel member of the family of tachykinins, evoked secretion from the three major salivary glands of the rat in the presence of muscarinic, alpha-adrenergic and beta-adrenergic receptor blockade; the submaxillary glands contributed most and the sublingual glands least to the total volume secreted. SK was less potent than substance P (SP) in evoking fluid and amylase secretion. However, the amylase concentration in parotid saliva evoked by SK was twice that evoked by SP, a finding which indicates that in the glands there are more than just one type of tachykinin receptors. Vasoactive intestinal peptide enhanced the SK evoked fluid response and increased the amylase concentration in parotid saliva. SK is a possible transmitter involved in the atropine-resistant parasympathetic nerve evoked salivation in the rat.
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PMID:Substance K and salivary secretion in the rat. 243 50

When rat parotid explants were cultured on siliconized lens paper floating on chemically defined 199 medium, all of sialagogues tested increased ornithine decarboxylase activity, which was roughly proportional to the amylase released into the culture medium. S-Adenosylmethionine decarboxylase and DNA synthesis were also induced by isoproterenol, methoxamine, carbachol and pilocarpine, but not by serotonin or substance P. The increases of the two decarboxylase activities and DNA synthesis were observed in vivo in mouse parotid gland after repeated injections of carbachol or pilocarpine. These results indicate that both adrenergic and cholinergic sialagogues stimulate the syntheses of polyamines and DNA in murine parotid gland.
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PMID:Effects of sialagogues on the syntheses of polyamines and DNA in murine parotid gland. 243 23

In the rat parotid gland, an atropine-resistant parasympathetic-nerve-evoked secretion was demonstrated in vivo. In the absence of atropine, the non-adrenergic, non-cholinergic transmitter release seemed to contribute to the fluid secretion and to be largely responsible for the secretion of amylase and acinar secretory granules. The gland was reached by nerve fibers containing substance P (SP), vasoactive intestinal peptide (VIP), and, to some extent, calcitonin-gene-related peptide (CGRP) via the parasympathetic auriculo-temporal nerve. Upon electrical stimulation of the nerve, these peptides were released. SP and substance K (SK), a novel tachykinin, induced a profuse watery secretion when injected i.v., while VIP caused a sparse but amylase-rich secretion. CGRP caused no secretion on its own. The tachykinin-evoked secretory response was enhanced by VIP and CGRP. A SP-analogue almost abolished the SP-evoked response, while the atropine-resistant parasympathetic response was only halved. None of the peptides under study can on its own account for the atropine-resistant parasympathetic secretion. The neuropeptides may play complementary roles in the regulation of the exocrine functions of the gland.
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PMID:Neuropeptides and secretion. 244 19

1. A modified continuous assay of alpha-amylase is detailed and its usefulness in measuring amylase secretion from rat parotid salivary gland described. 2. The alpha-amylase secretion from the rat parotid gland can be evoked by acetylcholine, substance P and isoprenaline. 3. The secretion of amylase was greatest following isoprenaline stimulation and was of a slower time course than with the other two agonists.
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PMID:Description of an automated assay for measurement of alpha-amylase in vitro from rat parotid gland slices. 244 21

Substance P, forskolin and isoprenaline stimulated rat parotid alpha-amylase secretion in vitro. Synergistic responses were observed with combinations of any two of the three secretagogues such that subthreshold doses of one caused a pronounced shift in the dose-response curve to the second. This potentiation of secretion could neither be explained by an interaction at the receptor recognition binding site, as identified by ligand binding, nor wholly by interactions in second messenger systems. Thus forskolin and isoprenaline were unable to alter substance P-induced changes in phosphatidylinositol metabolism. Similarly substance P was without effect on forskolin or isoprenaline-stimulated cAMP production. In contrast the potentiation of isoprenaline-induced amylase secretion by forskolin was preceded by a marked enhancement of cAMP production suggesting that the activation of the adenylate cyclase complex is reflected in the cellular response.
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PMID:Synergistic interactions between forskolin, isoprenaline and substance P as secretagogues in rat parotid glands. 245 34

Each peptide bond CONH group in the most important COOH-terminal octapeptide region of [Leu14]bombesin was replaced by a CH2NH group using recently developed rapid solid-phase methods. The resulting analogues were then examined for amylase releasing activity in guinea pig pancreatic acini and for their ability to inhibit binding of [125I-Tyr4]bombesin to acinar cells. Replacement of the Trp8-Ala9, Gly11-His12, and His12-Leu13 peptide bonds resulted in about 1000-, 200-, and 300-fold losses in both amylase releasing activity and binding affinity. The Val10-Gly11 replacement, however, retained 30% potency relative to the parent peptide. Ala9-Val10 and Leu13-Leu14 bond replacement analogues exhibited no detectable amylase releasing activity but were still able to bind to acini with Kd values of 1060 and 60 nM, respectively (compared to 15 nM for [Leu14]bombesin itself). Subsequently, both analogues were demonstrated to be competitive inhibitors of bombesin-stimulated amylase release with IC50 values of 937 and 35 nM, respectively. [Leu14-psi-CH2NH-Leu13]Bombesin exhibits a 100-fold improvement in binding affinity compared to previously reported bombesin receptor antagonists and showed no affinity for substance P receptors. It was also a potent inhibitor of bombesin-stimulated growth of murine Swiss 3T3 cells with an IC50 of 18 nM. In terms of a bombesin receptor-binding conformation, these results may aid in the delineation of intramolecular hydrogen-bonding points and the eventual design of improved, conformationally restricted analogues.
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PMID:Probing peptide backbone function in bombesin. A reduced peptide bond analogue with potent and specific receptor antagonist activity. 245 61

Although certain prostaglandins have been found to be inhibitory to nerve-evoked salivary flow, little is known of the effects the leukotrienes on salivary secretion. It was the purpose of this investigation to examine the effects of leukotrienes C4 (LTC4) and D4 (LTD4) on salivary secretion in the rat, using methacholine or substance P to induce basal secretion, and to test whether or not the observed effects of these eicosanoids were receptor-mediated by using the leukotriene receptor blocker FPL-55712. Methacholine (3 x 10(-4) M), or substance P (1 x 10(-6) M) was infused intra-arterially to stimulate secretion and saliva was collected separately from the parotid gland and the submandibular gland of anesthetized rats. LTC4 and LTD4 (each at 1 x 10(-9) to 1 x 10(-6) M) were found to reduce methacholine- and substance P-induced salivary flow in a dose-related manner. Salivary protein concentration and amylase activity were not significantly altered by the leukotrienes; however, arginine-esterase activity, stimulated by substance P, was increased by both leukotrienes. FPL-55712 (1 x 10(-8) M) was shown to reduce the inhibitory effects of LTC4 and LTD4, suggesting the involvement of leukotriene receptors for these agents in their action.
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PMID:The modulatory effects of leukotrienes C4 and D4 on methacholine- and substance P-induced salivary secretion in rats. 245 57


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