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)

Calmodulin present in rat parotid homogenates activated cyclic AMP phosphodiesterase activity by 8 to 10 fold. The activation was Ca2+-dependent and reversed by trifluoperazine. Half-maximal inhibition required 12 microM trifluoperazine. Incubation of parotid slices with up to 40 microM trifluoperazine had no effect on the basal rate of amylase and K+ release or on cellular ATP content. Isoproterenol stimulated glucose utilization and substance P stimulated amylase secretion were also unaffected by 40 microM trifluoperazine. 20 or 40 microM Trifluoperazine however inhibited amylase secretion induced by isoproterenol, dibutyryl cyclic AMP, carbamoylcholine or phenylephrine. The possible involvement of calmodulin in regulating enzyme secretion following stimulation of the parotid gland with the various types of agonists is discussed.
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PMID:Does calmodulin mediate stimulus-secretion coupling in the parotid gland? Studies using trifluoperazine. 620 27

Intracellular recordings were obtained from neurones of isolated guinea-pig inferior mesenteric ganglia. Repetitive stimulation (10-20 Hz for 1-2 s) of the hypogastric nerves evoked, in addition to the fast excitatory post-synaptic potential (e.p.s.p.), a non-cholinergic e.p.s.p. the mediator of which has previously been suggested to be substance P or a related peptide. When applied to the ganglia in the concentrations of 1-100 microM for 3-5 min, adrenaline, isoprenaline and noradrenaline produced an initial, short-lasting depression which was followed by a marked augmentation of the non-cholinergic e.p.s.p. lasting from minutes to over hours. Employed in comparable concentrations dopamine caused a slight depression that was not followed by a detectable increase of the non-cholinergic e.p.s.p. The catecholamine-induced depression and subsequent enhancement of the non-cholinergic e.p.s.p. was prevented by alpha-adrenergic antagonists (dihydroergotamine and phenoxybenzamine, 1-10 microM) and beta-adrenergic antagonists (propranolol and dichlorisoprenaline, 5-10 microM), respectively. The membrane depolarization induced by the putative transmitter substance P (1 microM) was augmented by isoprenaline; the enhancement which could be blocked by beta-antagonists was not preceded by a depression. Application of dibutyryl cyclic AMP (10 microM-1 mM) by either superfusion or intracellular ionophoresis mimicked the enhancing effect of catecholamines. It is concluded that catecholamines, with the noticeable exception of dopamine, exerted a biphasic effect on the non-cholinergic e.p.s.p. of the inferior mesenteric ganglion cells: an initial depression that was mediated by alpha-adrenergic receptors and probably reflected a presynaptic inhibitory effect of catecholamines and, on the other hand, an enduring facilitation mediated by beta-adrenergic receptors which appeared to be linked to activation of post-ganglionic cyclic AMP.
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PMID:Long-term facilitation of peptidergic transmission by catecholamines in guinea-pig inferior mesenteric ganglia. 621 Mar 57

Vasoactive intestinal peptide (VIP) has been shown to increase cyclic AMP content in isolated epithelial cells of rat ventral prostate. The stimulatory effect of VIP was dependent on time and temperature and was potentiated by a phosphodiesterase inhibitor. At 15 degrees C, the response occurred in the 1 X 10(-10)-10(-7)M range of VIP concentrations. Half-maximal stimulation of cellular cyclic AMP was obtained at 1.4 nM and maximal stimulation (3-fold basal level) at about 100 nM VIP. Chicken VIP and porcine secretin were agonists of porcine VIP but exhibited a 2-times higher and a 170-times lower potency, respectively. A high concentration (1 X 10(-6)M) of glucagon, somatostatin, neurotensin, substance P, Met-enkephalin or Leu-enkephalin did not modify cAMP levels. The finding of a VIP-stimulated cAMP system in rat prostatic epithelial cells together with the previous characterization of high-affinity receptors for VIP in the same cell preparation, as well as the presence of VIP-containing neurones innervating the male genitourinary tract, strongly suggest that VIP may be involved in prostatic growth regulation and function.
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PMID:Cyclic AMP-stimulating effect of vasoactive intestinal peptide in isolated epithelial cells of rat ventral prostate. 631 52

Since VIP occurs in intrathyroidal nerves its role in thyroid hormone secretion has been investigated. It has been found that VIP is a stimulator of iodothyronine secretion in mice. In this respect VIP has a weaker potency than TSH, but shows a similar time characteristic. Also, VIP and TSH potentiate each others effects. In contrast to the effect of TSH, that of VIP is uninfluenced by alpha-adrenoceptor blockade. VIP, like TSH, stimulates thyroid cyclic AMP production. Thus, VIP nerves might, together with TSH, adrenergic and cholinergic nerves and other peptides such as somatostatin, participate in the complex regulation of iodothyronine secretion. Beside this, VIP has also been found to stimulate calcitonin secretion in rats. Other intrathyroidal neuropeptides, such as substance P and CCK-4, have been found to be without effects on iodothyronine secretion, but, like VIP, to stimulate calcitonin secretion.
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PMID:Influence of VIP on thyroid hormone secretion. 647 58

Effects of substance P on cultured neurons of the locus coeruleus of the rat were studied using the whole-cell patch clamp technique. In some cells substance P produced a decrease in a K conductance which showed an inwardly rectifying property. In other cells substance P produced an initial inward current which was accompanied by a conductance increase. The rest of the cells showed responses which were mixtures of the above two responses. The measurement of the reversal potential of the initial inward current after suppressing the voltage-gated Ca and K conductances suggests that it is caused by an increase in a non-selective ionic conductance. In cells loaded with 260 microM GTP gamma S, application of substance P produced an irreversible reduction of the K conductance, while the initial inward current could still be recorded, suggesting that the former is mediated by a G protein, whereas the latter may be activated by a different signal transduction mechanism. The initial inward current was not eliminated by external application of high concentrations of tetrodotoxin, d-tubocurarine or amiloride. Nor was it affected by the intracellular application of cyclic GMP or cyclic AMP.
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PMID:Two signal transduction mechanisms of substance P-induced depolarization in locus coeruleus neurons. 750 20

1. In helical strips of dog superficial temporal arteries with intact endothelium, substance P elicited a concentration-related relaxation with an EC50 of 2.8 (2.4-3.2) x 10(-10) M. 2. The relaxant response to the peptide in low concentrations (1-4 x 10(-10) M) sufficient to produce approximately half maximal relaxation was not inhibited by indomethacin, but was markedly suppressed by NG-nitro-L-arginine (L-NOARG), a nitric oxide (NO) synthase inhibitor, and by endothelium denudation. 3. High concentration (10(-7) M) of substance P produced marked relaxations in endothelium-intact strips. Removal of the endothelium attenuated the relaxation, and indomethacin or tranylcypromine suppressed the endothelium-independent relaxation. In indomethacin-treated strips with intact endothelium, L-NOARG attenuated but did not abolish the relaxation. The residual, L-NOARG-resistant relaxation was not significantly inhibited by ouabain, glibenclamide or tetraethylammonium. 4. Substance P (10(-7) M) increased the levels of cyclic GMP and cyclic AMP. The increase in cyclic GMP was abolished by endothelium denudation and treatment with L-NOARG, whereas the cyclic AMP increment was abolished by indomethacin. 5. Three different mechanisms may be involved in the substance P-induced relaxation: (1) an endothelium-dependent relaxation mediated by the release of NO from the endothelium, resulting in an increase of cyclic GMP (low and high concentrations of the peptide); (2) an endothelium-independent relaxation in association with cyclic AMP increment caused by prostaglandin I2 released from subendothelial tissues (high concentration), and (3) another endothelium-dependent relaxation possibly mediated by unidentified mediator(s) released from the endothelium (high concentration).
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PMID:Mechanism underlying substance P-induced relaxation in dog isolated superficial temporal arteries. 751 4

1. The whole cell patch clamp was used to measure calcium current in isolated chick sympathetic ganglion neurons. Previous results showed that somatostatin inhibits calcium currents (ICa) in a voltage-dependent manner. The effect of somatostatin rapidly desensitizes. In addition, the action of somatostatin on the calcium current is inhibited by activation of protein kinase C (PKC). Because substance P (SP) has been shown to activate PKC in the chick sympathetic neurons, we here test the effects of SP on the calcium current and on the modulatory action of somatostatin. 2. At a concentration of 1 microM, SP had small, variable effects on ICa. 3. SP in the presence of guanosine 5'-triphosphate-gamma-S, or at higher concentrations (10 microM), inhibited ICa in a voltage-dependent manner, similar to the action of somatostatin. 4. Rather than inhibiting the action of somatostatin, SP (1 microM) potentiated the response to somatostatin. This effect of SP was only observed after the response to somatostatin had partially desensitized. SP had no effect on nondesensitized responses to somatostatin. 5. Desensitization of the somatostatin response involved a shift in its dose-response curve toward higher somatostatin concentrations as well as a decrease in the maximal response. SP appears to counteract the shift of the dose-response curve selectively. 6. The potentiation of the somatostatin response by SP is blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), but not by Calphostin C, Compound 5, k252a, protein kinase C (PKC)19-36, or adenylyl-imidodiphosphate (AMP-PNP), suggesting that phosphorylation is not involved and that the H-7 action does not depend on kinase inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substance P potentiates calcium channel modulation by somatostatin in chick sympathetic ganglia. 753 25

The mechanisms involved in 'priming' of the oxidase response of neutrophils are unknown. Two major problems are encountered in using circulating neutrophils; firstly, prior exposure to circulating 'priming' cytokines cannot be controlled and secondly, non-intentional 'priming' during cell separation can occur. In this study, these problems were avoided by differentiating the promyeloid leukaemic cell line, HL60, towards granulocytes using dibutyrl cyclic AMP, to produce a 'virgin cell' model system. We have demonstrated that the ability of substance P to both prime the oxidase response and induce tyrosine phosphorylation increased during differentiation. The major tyrosine-phosphorylated protein, with molecular weight of 74 kDa, was not recognised by anti-c-raf1 antibodies. Furthermore, c-raf1 expression rapidly declined during HL60 cell granulocytic differentiation. This data shows that although there was no simple relationship between c-raf quantity and priming, the data were consistent with tyrosine phosphorylation of a 74 kDa protein being important for oxidase 'priming'.
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PMID:Development of oxidase 'priming' in maturing HL60 cells: correlation with protein expression and tyrosine phosphorylation. 754 45

1. The responses of guinea-pig endocardial endothelial (EE) cells to various vasoactive substances were investigated in either the small tissue preparation or freshly isolated cells using the patch clamp technique. 2. The mean resting potential of the EE cell was -44 mV in the small tissue preparation, and applications of ATP, ADP, AMP, adenosine, histamine and substance P induced transient hyperpolarizations of -22, -21, -9, -10, -23 and -15 mV, respectively. The membrane potential of EE cells failed to respond to acetylcholine, bradykinin, thrombin, atrial natriuretic peptide, vasopressin and serotonin. 3. The whole-cell voltage clamp of dissociated cells revealed a transient increase of K+ conductance underlying the ATP and histamine responses. The agonist-induced current showed no time-dependent change during voltage steps. The response was showed no time-dependent change during voltage steps. The response was prevented by adding 10 mM EGTA to the pipette solution. 4. In the cell-attached single channel recordings, ATP induced transient K+ channel activities having a slope conductance of 34 pS. In inside-out patches, similar K+ channels were activated by applying Ca2+ of more than 0.1 microM. 5. These findings are consistent with the idea that the Ca(2+)-dependent K+ channel is involved in the hyperpolarizing response of EE cells, as described in vascular endothelial cells.
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PMID:Hyperpolarization induced by vasoactive substances in intact guinea-pig endocardial endothelial cells. 754 61

In order to determine whether nitric oxide (NO) acts directly upon nerve terminals to regulate the synaptic transmission at the level of spinal cord, effects of NO-donors on release of substance P (SP) and glutamic acid (Glu) were investigated by superfusion of synaptosomes prepared from the rat spinal cord. Basal levels of endogenous SP and Glu release were 5.99 +/- 2.50 fmol/min/mg of protein and 26.2 +/- 4.8 pmol/min/mg of protein, respectively. Exposure to a depolarizing concentration of KCI evoked 2.7- and 3.8-fold increases in SP and Glu release in a calcium-dependent manner, respectively. Sodium nitroprusside (NP) caused a reduction in the depolarization-evoked overflow of SP in a concentration-dependent manner without affecting its basal release, although it failed to affect either basal or evoked release of Glu. The reduction in SP overflow was also observed by the perfusion with S-nitroso-N-acetyl-penicillamine or membrane-permeable cyclic GMP, but not with cyclic AMP. NP caused the concentration-dependent increases in cyclic GMP levels in synaptosomes. Together with reports that excitatory amino acids stimulate NO synthase and release NO in the spinal cord, these data suggest that there may be an interaction between nerve terminals containing Glu and SP, and that NO may directly participate in the regulation of synaptic transmission in SP-containing nerve terminals, which may be mediated through the activation of guanylate cyclase and the increase in cyclic GMP levels.
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PMID:Nitric oxide regulates substance P release from rat spinal cord synaptosomes. 759 89


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