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)

First incubating guinea pig pancreatic acini with carbachol reduced the subsequent stimulation of amylase release caused by carbachol, cholecystokinin octapeptide (CCK-8), and bombesin but not that caused by vasoactive intestinal peptide, substance P, 8-bromoadenosine 3',5'-cyclic monophosphate, A23187, or 12-O-tetradecanoylphorbol-13-acetate. Carbachol also reduced the subsequent binding of N-[3H]methylscopolamine, 125I-CCK-8, and 125I-[Tyr4]bombesin. Pancreatic acini possess a high-affinity class of cholinergic receptors and a low-affinity cholinergic receptors appears to produce the reduction in carbachol-stimulated amylase release and binding of N-[3H]methylscopolamine. First incubating acini with carbachol caused a complete loss of high-affinity cholinergic receptors with no change in the number or affinity of low-affinity cholinergic receptors. Carbachol occupation of low-affinity cholinergic receptors appears to produce the reduction in CCK-8- and bombesin-stimulated amylase release and in binding of 125I-CCK-8 and 125I-[Tyr4]bombesin. Acini possess two classes of CCK receptors. One class has a high affinity for CCK-8; the other class has a low affinity for CCK-8. First incubating acini with carbachol caused a 60% decrease in the number of high-affinity CCK receptors with no change in the number of low-affinity receptors or the affinities of either class of receptors for CCK-8. Acini possess a single class of bombesin receptors, and first incubating acini with carbachol caused a 40% decrease in the number of bombesin receptors with no change in their affinity for bombesin. 12-O-tetradecanoyl phorbol-13-acetate reproduced the action of carbachol on binding of N-[3H]methylscopolamine and 125I-CCK-8 but not on binding of 125I-[Tyr4]bombesin, suggesting that carbachol activation of protein kinase C may in some way mediate the effect of carbachol on receptors for carbachol and those for CCK but not that on receptors for bombesin.
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PMID:Carbachol desensitizes pancreatic enzyme secretion by downregulation of receptors. 168 17

Two novel neuromedin C analogs [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C and [Leu9-psi-CH2NH-Leu10]neuromedin C, were synthesized by rapid solid phase methods and examined for their abilities to inhibit neuromedin C-stimulated amylase release by isolated rat pancreatic acini. Both analogs significantly inhibited maximally stimulated amylase release by neuromedin C in a dose-dependent manner with maximal inhibition seen at concentrations of 100 and 300 microM of [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C and [Leu9-psi-CH2NH-Leu10]neuromedin C, respectively. The IC50 (concentration required to half-maximally inhibit neuromedin C-stimulated amylase release) was 1.5 microM for [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C compared to a 13.4 microM IC50 for [Leu9-psi-CH2NH-Leu10]neuromedin C. The [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C analog produced a parallel rightward shift in the neuromedin C dose-response curve and Schild plots of the inhibition data gave a slope of 0.969 +/- 0.121 and a pA2 (apparent affinity for the acinar cell receptor in terms of neuromedin C receptor-stimulated amylase release) of 100 nM. While [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C significantly inhibited both neuromedin B- and gastrin releasing peptide-stimulated amylase release, the analog did not inhibit amylase release in response to either cholecystokinin octapeptide, vasoactive intestinal peptide, substance P, carbamylcholine, the Ca2+ ionophore A23187, forskolin, or 8-bromo-cyclic AMP. The results demonstrate that [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C is a potent, specific, and competitive antagonist for neuromedin C and peptides of the gastrin releasing peptide family and may serve as a useful molecule for exploring the physiological role of these peptides.
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PMID:[D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C antagonizes neuromedin C-stimulated amylase release by acini isolated from the rat pancreas. 169 79

The kinetics of the changes in the cytoplasmic Ca2+ concentration (Ca2+i) and amylase release were measured in fura-2-loaded pancreatic acinar cells and perifused pancreatic acini, respectively. Cholecystokinin octapeptide (CCK-8) and its amphibian analogue caerulein induced similar dose-related increases of Ca2+i and amylase secretion with threshold concentrations of 2-6 x 10(-12) M, and maximal effects at 2 x 10(-10) M. The action of CCK/caerulein on Ca2+i was complex and similar to that of carbachol and bombesin with a prompt several-fold increase within seconds followed by a gradual decline over more than 5 min to a new sustained suprabasal level. The kinetics of amylase release in response to CCK and carbachol correlated with the changes in Ca2+i. Additions of the antagonists N2,O2-dibutyrylguanosine 3':5'-cyclic monophosphate and atropine after 30 min of CCK-8 and carbachol stimulation, respectively, were associated with prompt lowerings of Ca2+i and inhibitions of amylase secretion. The patterns observed with substance P (SP) and eledoisin were different with high concentrations (10(-8)-10(-7) M) giving monophasic increases of Ca2+i and amylase release. An initial stimulation of cells with a high dose of CCK eliminated the Ca2+i response to further stimulation with CCK, carbachol, bombesin and SP, whereas cells subjected to initial stimulation with SP responded to subsequent exposure to CCK with prolonged elevation of Ca2+i. The data indicate that stimulation with CCK, carbachol and bombesin may be associated with intracellular mobilization of calcium from more than one pool, and that an increase of Ca2+i is involved even in threshold stimulation of amylase release.
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PMID:Stimulation of pancreatic amylase release is associated with a parallel sustained increase of cytoplasmic calcium. 170 10

The effect of barium on isolated acini was tested. Barium in the 0.1-10 mM concentration range non-competitively inhibited the efflux of 86Rb+ stimulated by carbamylcholine or substance P. This inhibition was independent of the presence of calcium in the extracellular medium. In the same preparation, barium did not affect the efflux of 45Ca2+ but, at a 10 mM concentration, it increased amylase release by 70%. Removal of extracellular calcium decreased basal amylase release and the response to carbamylcholine. Adding back calcium or barium to the incubation medium increased basal and carbamylcholine-stimulated amylase secretion, but calcium was more effective than barium. These results suggest that barium has two opposite effects on calcium-regulated processes in rat parotid gland: (1) it is an inhibitor of calcium-activated potassium channels; (2) it is a partial agonist of calcium-activated amylase secretion.
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PMID:Response of rat parotid acini to barium. 171 13

Intralobular (granular) salivary ducts were purified by isopycnic centrifugation after collagenase/hyaluronidase digestion of the rat submandibular gland. The resulting ductal fraction (density, 1.056 +/- 0.003) was highly enriched in kallikrein (a ductal cell marker) and contained little amylase activity (an acinar cell marker). The resting intracellular calcium level in the ductal preparation was 103 +/- 4 nM. Increased intracellular calcium concentrations (2-3 times resting levels) were observed in response to muscarinic (carbachol) and alpha-adrenergic (epinephrine) agonists, but little response was observed to substance P, suggesting the absence of substance P peptidergic receptors on rat submandibular ducts. Intracellular adenosine 3',5'-cyclic monophosphate levels were increased 35-fold in response to beta-adrenergic stimulation (isoproterenol) and forskolin. The ducts secreted kallikrein in response to epinephrine, carbachol, and isoproterenol but not in response to substance P. Epinephrine was the most potent inducer of kallikrein release with a K0.5 of approximately 3 microM and a maximal secretory rate approximately nine times unstimulated levels. Taken together, these results provide strong evidence for the functional integrity of the ductal preparation. This preparation should prove useful for the further elucidation of the properties of intralobular salivary ducts structures which heretofore have only been studied indirectly.
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PMID:Isolation and characterization of rat submandibular intralobular ducts. 171 52

Isolated parotid acinar cells were perifused in small columns by embedding them in Bio-Gel P-2 beads as an inert supporting matrix, and the effect of carbamylcholine, substance P, and isoproterenol on the rate of amylase release was examined by measuring amylase activity in the effluent. Amylase release by continuous stimulation with carbamylcholine and substance P was biphasic. They caused a rapid and large increase in the rate of amylase release that reached maximum 30 to 60s after the onset of stimulation, followed by a rapid decline to a lower sustained level that was maintained as long as the agonists were present. The rapid decline in the rate of amylase release was due to rapid development of refractoriness. Repeated 1 min pulse stimulation with these secretagogues showed that recovery from refractoriness was also rapid in onset, and 1 min of washout was sufficient to cause significant recovery from refractoriness for both carbamylcholine and substance P. Recovery, however, was not complete after 10 min of washout. Amylase release by continuous stimulation with isoproterenol, on the other hand, developed more slowly with the peak rate being attained at about 6 min after the onset of stimulation. Refractoriness was not observed in the effect of isoproterenol. The maximum effect in the rate of amylase release attained by carbamylcholine or substance P was higher than that by isoproterenol. These results suggest that the apparent small effect of carbamylcholine and substance P on amylase release reported earlier by using batch systems is probably due to the rapid development of refractoriness to these secretagogues, but not to isoproterenol.
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PMID:Dynamic changes in the rate of amylase release induced by various secretagogues examined in isolated rat parotid cells by using column perifusion. 172 Apr 73

Although bombesin (BN) and substance P share only the C-terminal dipeptide amide, some substance P receptor antagonists are also weak bombesin receptor antagonists. In order to increase the selectivity of the antagonism for the BN receptor, a series of hybrid peptides were synthesized by the solid-phase methodology, and screened on 3T3 fibroblasts for binding and mitogenic activity. The analogues inhibiting BN-induced thymidine incorporation were further tested for peripheral (amylase release and urinary bladder contraction) and central activity (grooming behaviour).
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PMID:Bombesin receptor antagonists. 2. Analogues based on substance P antagonists. 172 78

1. Cytoplasmic Ca2+ ([Ca2+]i) responses were studied in guinea-pig pancreatic acinar cells during stimulation with cholecystokinin octapeptide (CCK-8), substance P (SP) and carbachol. 2. Individual cells exhibited [Ca2+]i responses to all three agonists. 3. In the absence of external Ca2+, all the agonists initiated [Ca2+]i peaks which, particularly at high agonist concentrations, rapidly declined. 4. SP induced repetitive monophasic [Ca2+]i transients which started from basal [Ca2+]i even after elevation of the external Ca2+ concentration. 5. CCK-8 triggered similar oscillations, which particularly at high agonist concentration or after elevating external Ca2+ became superimposed upon a sustained elevation of [Ca2+]i. 6. Carbachol-induced oscillations were more complex with [Ca2+]i transients superimposed on slower waves. 7. At high carbachol concentrations or elevation of external Ca2+ the slow waves fused into a sustained increase of [Ca2+]i. 8. The protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate attenuated the agonist-induced [Ca2+]i responses, and this effect was reversed by the PKC activator staurosporine. 9. The results indicate that oscillations of [Ca2+]i induced by SP, CCK-8 and carbachol involve intracellular mobilization of Ca2+. 10. CCK-8 and carbachol also cause a rise of [Ca2+]i by a mechanism more directly dependent on the presence of extracellular Ca2+. 11. In the case of carbachol the latter component is subject to oscillatory control. 12. The transition from oscillatory [Ca2+]i to sustained increase may be associated with inhibition of amylase release.
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PMID:Calcium oscillations in guinea-pig pancreatic acinar cells exposed to carbachol, cholecystokinin and substance P. 172 99

In rats the parasympathetic auriculo-temporal nerve on one side was continuously stimulated at 40 Hz for 20-80 min in the presence of adrenergic blockers (dihydroergotamine and propranolol) +/- atropine. During the first 10 min this gave rise to a flow of saliva from the parotid gland that in the atropinized rats amounted to 35% of that found in rats not treated with atropine, while the protein and amylase outputs were 75% of those in non-atropinized rats. The atropine-resistant secretion of fluid and proteins declined to 5-10% of the initial value within 40 min but did not cease completely even after 80 min. The marked reduction in secretory responses was not due to desensitization or exhaustion of the gland cells. The nerve stimulation reduced the parotid gland content of vasoactive intestinal peptide (VIP) and substance P (SP) to approximately 60 and 25% of that of contralateral glands after 20 and 60 min, respectively. The probable explanation for the decline in secretory response seems to be depletion of non-adrenergic, non-cholinergic transmitter(s). The present results suggest that neuropeptides are involved in the regulation of salivary secretion but provide no direct evidence that either VIP or SP is responsible for the atropine-resistant salivary secretion.
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PMID:Depletion of neuropeptides in rat parotid glands and declining atropine-resistant salivary secretion upon continuous parasympathetic nerve stimulation. 241 6

A pancreatic acinar cell line, AR4-2J, that expresses a high density of substance P (SP)-binding sites has been identified. SP-binding sites on intact AR4-2J cells were detected with 125I-Bolton-Hunter SP (125I-BHSP). 125I-BHSP binding to AR4-2J cells has an apparent Kd of 40 pm with slow rates of association and dissociation. The number of high affinity binding sites was about 10(4)/cell. Binding of 125I-BHSP was inhibited by SP and by structurally related peptides. Physalaemin was a more potent inhibitor of binding than SP, whereas kassinin, eledoisin, and neurokinin A (substance K, neuromedin alpha, or neurokinin L) were much less potent. SP-free acid and SP (7-11) were 3 to 4 orders of magnitude less potent than SP itself. The membrane, intracellular, and secretory events elicited by exposure of AR4-2J cells to SP have also been examined. Intracellular recording from AR4-2J cells revealed resting membrane potentials of -40 to -65 mV. Pressure application of SP (100 pM to 100 nM) evoked depolarizations of 20 to 40 mV which were maintained for prolonged periods. The intracellular free calcium concentration in AR4-2J cells, measured with (2-[2-amino-5-methylphenoxy)-methyl)-6-methoxy-8-aminoquinolone tetra-acetoxy methyl ester), was between 100 and 500 nM. Addition of SP (100 pM to 10 nM) or physalaemin (1 nM) induced a transient rise in intracellular free calcium. AR4-2J cells synthesize amylase, and exposure of cells to SP resulted in a dose-dependent increase in amylase secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional substance P receptors on a rat pancreatic acinar cell line. 241 93


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