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)

Functional and specific receptors for vasoactive intestinal peptide (VIP) (determined by their capacity to bind 125I-VIP and activate adenylate cyclase) and cyclic AMP-dependent phosphodiesterase activities were characterized in enterocytes of human fetal small intestine between 18 and 23 weeks of gestation. Half-maximal stimulation of the cyclase and inhibition of 125I-VIP binding in membrane preparations were respectively observed at 1.4 and 5 X 10(-10) M VIP. The peptides structurally related to VIP activated the cyclic AMP generating system at pharmacological doses (10(-7) M and above) in the following order of potency: VIP greater than PHI greater than GRF greater than secretin. Other peptides or test substances, including GIP, pancreatic glucagon, somatostatin-14, gastrin, CCK, neurotensin, pancreatic polypeptide, PYY, substance P, histamine and isoproterenol are inactive in this system, while the ubiquitous adenylate cyclase activators NaF, forskolin and prostaglandins were effective. These results, combined with the appearance of intestinal VIP in nerve fibers at 8 weeks and with the morphological and enzymatic maturation at 9-12 weeks of the intestinal mucosa, indicate that this neuropeptide may regulate either the differentiation or function of enterocytes during the early development of human intestinal mucosa.
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PMID:Vasoactive intestinal peptide receptor activity in human fetal enterocytes. 298 18

The intracellular adenine nucleotide pool of rabbit iris-ciliary body was labelled by uptake of 3H-adenine in vitro. A variety of agents were tested for their ability to stimulate or inhibit the incorporation of radioactivity into cyclic AMP formed from ATP labelled with 3H-adenine. Isoproterenol, vasoactive intestinal peptide, forskolin, and prostaglandin E2 stimulated incorporation of label 3-10-fold in 15-20 min compared with paired tissues not treated with hormone, whereas histamine, serotonin, substance P, and bradykinin were inactive. Clonidine, alpha-methylnorepinephrine, and dopamine decreased the rate of incorporation of label into the cyclic-AMP pool in tissues that showed high spontaneous basal rates. In low-basal tissues these drugs were inactive by themselves but clonidine and alpha-methylnorepinephrine blocked the stimulation effected by isoproterenol. The findings indicate that several receptor-coupled adenylate cyclase systems are present in ICB and that dual adrenergic control of adenylate cyclase through positive and negative coupling of adrenergic receptors probably occurs. The negatively coupled adrenergic receptors appear to be similar to the alpha 2-subclass of adrenergic receptor described in other tissues. These observations suggest a role for the large number of alpha 2-adrenergic-binding sites found in albino rabbit iris-ciliary body by ligand binding assays.
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PMID:Drug responses of adenylate cyclase in iris-ciliary body determined by adenine labelling. 298 54

Classical techniques for studying modulations of microvascular permeability have a time resolution of minutes. A newly developed method allows continuous measurement of the electrical resistance of the microvascular membrane in vivo (Olesen & Crone 1983). The technique exploits microelectrodes impaled into the vascular lumen and is based on cable analysis of the vessel. It was applied to venules on the surface of the frog brain to test the effect on microvascular permeability of a wide variety of substances. The following agents increased ionic permeability reversibly within seconds: 5-hydroxytryptamine, bradykinin, ATP, ADP, AMP, phospholipase A2, arachidonic acid, leukotriene C4, oxygen-derived free radicals, ionophore A23187, and unbound Evans blue dye. An irreversible permeability increase was induced by protamine sulphate, neuraminidase, trypsin, melittin, and snake venoms from Crotalus durissus terrificus and Bothrops atrox. The following substances were without effect within an administration period of 5 min: histamine, epinephrine, putrescine, angiotensin II, vasoactive intestinal polypeptide (VIP), substance P, neurotensin, vasopressin, adenosine, PGE2, PGF2 alpha, prostacyclin (PGI2), leukotriene B4, albumin, heparin, plant cytokinins, hyaluronidase, thrombin, wasp venom. Variations in pH between 5.1 and 8.6 did not change permeability. Three conclusions are drawn from the observations: (1) the permeability of cerebral microvessels can be modulated by specific agents, (2) the agents induced changes in the endothelium within a few seconds, and (3) the rapid permeability increase induced by inflammatory mediators was less than two-fold and reversible within minutes.
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PMID:Substances that rapidly augment ionic conductance of endothelium in cerebral venules. 348 16

1. The biogenic amines 5-hydroxytryptamine (5-HT) and histamine, and the peptides bombesin, gastrin-releasing peptide (GRP), vasoactive intestinal peptide (VIP), cholecystokinin (CCK), substance P and calcitonin gene-related peptide (CGRP) each mimicked slow synaptic excitation (slow e.p.s.p.) when applied to myenteric neurones of the guinea-pig small intestine. 2. Stimulation of the catalytic activity of adenylate cyclase by forskolin and intraneuronal elevation of cyclic 3',5'-adenosine monophosphate (cyclic AMP) also mimicked the slow e.p.s.p. and the actions of the aminergic and peptidergic messengers. 3. Adenosine prevented stimulation of adenylate cyclase by forskolin and abolished the slow e.p.s.p.-like actions of forskolin. 4. Exposure of the neurones to adenosine prior to or during application of bombesin, GRP, VIP, CCK or histamine blocked the actions of these substances. 5. Pre-treatment with adenosine did not suppress the slow e.p.s.p.-like actions of substance P, CGRP or 5-HT. 6. The results suggest that signal transduction for bombesin, GRP, VIP, CCK and histamine involves stimulation of adenylate cyclase and second messenger function of cyclic AMP. Transduction mechanisms for 5-HT, substance P and CGRP appear not to involve second messenger function of cyclic AMP.
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PMID:Transduction of aminergic and peptidergic signals in enteric neurones of the guinea-pig. 365 77

In muscularis mucosae from the opossum distal colon, both tone and spontaneous contractions were highly dependent on the available oxygen. Acetylcholine and histamine caused, respectively, atropine- and pyrilamine-sensitive contractions. Norepinephrine relaxed the tissue, an effect abolished by propranolol. Under these conditions norepinephrine failed to elicit contractions and at higher concentrations again caused relaxations. The tissue gave concentration-dependent relaxations to ATP but not to ADP, AMP, or adenosine. Electrical field stimulation (20-30 Hz, 1-2 ms, 120 mA) revealed a cholinergic excitatory innervation and a nonadrenergic, noncholinergic neural inhibition. Cholecystokinin, gastrin, substance P, and vasoactive intestinal polypeptide were without effect on this tissue. In these respects, colonic muscularis mucosae differs considerably from that of other gastrointestinal viscera.
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PMID:Pharmacological characterization of opossum distal colonic muscularis mucosae in vitro. 394 17

Two cell culture systems were used for studies of neural functions in vitro. A neuronal hybrid cell line (neuroblastoma x glioma hybrid cells) and primary glial-rich cultures of newborn murine brain. The level of cyclic AMP in both systems is regulated by two groups of hormones, those that stimulate and those that inhibit formation of cyclic AMP. Among the inhibitory hormones active on the hybrid cells are opioids. Therefore the cells are being used in the elucidation of action of opioids. The list of stimulating and inhibitory hormones regulating the primary glial-rich cultures includes several peptide hormones such as the gastrointestinal peptides secretin and vasoactive intestinal peptide, the calcaemic hormones parathyrin and calcitonin, adrenocorticotropin and melanotropins, and somatostatin. Noradrenaline (via alpha- and beta-adrenergic receptors) and adenosine (via A1 and A2 receptors) inhibit and stimulate cyclic AMP synthesis in the primary glial-rich cultures. Bradykinin slowly hyperpolarizes the hybrid cells and elicits formation of cyclic GMP. Both responses desensitize rapidly. Substance P increases the permeability of hybrid cells for Na+, as measured by using 14C-guanidinium as substitute for Na+. Hybrid cells actively accumulate taurine, an amino acid that appears to fulfill important functions in the nervous system. The transport of taurine across the plasma membrane is highly specific for and strictly dependent on Na+. The pumped station hypothesis of taurine action in the nervous system views taurine gradient plus taurine carrier as a transport system for the elimination of sodium from neurons during phases of high neuronal activity.
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PMID:Cell culture as models for studying neural functions. 608 74

The nicotinic acetylcholine receptor of Torpedo californica has been shown to be subject to cyclic AMP-dependent phosphorylation, raising the possibility that nicotinic receptors may be regulatable by phosphorylation. To investigate this possibility for a neuronal nicotinic receptor, we have studied the effects of elevation of cyclic AMP on the ion-conducting properties of the nicotinic receptor of PC12 cells. The cyclic AMP content of the cells was altered by exposure to various concentrations of forskolin (an activator of adenylate cyclase) for periods of time ranging from 1 to 40 min. Receptor activation then was measured as agonist-induced influx of 86Rb+ into the cells. Throughout a variety of conditions, no changes in agonist-induced ion influx were detected. This was true regardless of the concentration of agonist used, the duration of receptor stimulation that was measured, the concentration of forskolin employed, or the duration of elevation of cyclic AMP prior to receptor activation. Experiments designed to measure receptor desensitization also were unable to detect any differences upon elevation of cyclic AMP. Finally, the antagonism of receptor activation by substance P also was not affected by elevation of cyclic AMP. Thus, no evidence could be obtained in these cells supporting the hypothesis that a neuronal nicotinic acetylcholine receptor can be acutely regulated by changes in cellular cyclic AMP.
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PMID:Acute elevation of cyclic AMP does not alter the ion-conducting properties of the neuronal nicotinic acetylcholine receptor of PC12 cells. 608 18

F9 line embryonal carcinoma cells were induced to differentiate into neural direction by long-term treatment of monolayer cultures with retinoic acid and dibutyryl cyclic AMP. Bi- and multi-polar cells appeared, expressing acetylcholinesterase and neurofilament proteins but not markers of glial differentiation including GFA-protein. Nerve growth factor combined with both retinoic acid and dibutyryl cyclic AMP greatly enhanced the development of neuron-like morphology and induced expression of immunoreactivity to tyrosine hydroxylase as well as to Leu-encephalin-like peptides. Similarly, serotonin-like immunofluorescence but not substance P-like immunoreactivity was demonstrable in such cultures. In addition, synaptic-like vesicles were often found in the processes. Analysis of matrix expression in neuronally differentiated F9 cells revealed marked increase in laminin production, as judged by immunofluorescence and immuno-electron microscopy, but no demonstrable intracellular staining for fibronectin or type IV collagen. The results with neuronal cells contrast with the expression of all the three matrix components in endodermally differentiating F9 cells in the same cultures.
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PMID:Neuronal differentiation in F9 embryonal carcinoma cells. 610 Jan 70

The effects of a number of vasoactive and neurotransmitter substances on lymphocyte traffic were studied by assessing their effects on the release of lymphocytes into primary peripheral (popliteal) nodal efferent lymph of sheep following acute infusion into cannulated afferent nodal lymphatics. In a total of 23 experiments, the output of lymphocytes, small and blast, was increased by serotonin, substance P, bombesin, [met]enkephalin, isoprenaline and phenylephrine and was decreased by vasoactive intestinal peptide (VIP), neurotensin and carbachol. Substances whose actions are modulated by prostaglandins and enhanced by prostaglandin synthesis inhibitors and which elevate blood monocyte and nervous tissue levels of cyclic GMP tended to increase lymphocyte traffic through peripheral lymph nodes in sheep in vivo. The opposite effect tended to be produced by substances whose actions require or are associated with prostaglandins or histamine, and which affect blood monocytic cyclic nucleotide levels by elevation of cyclic AMP or depression of cyclic GMP. Pain and inflammation tended to increase lymphocyte traffic, while analgesics and immunomodulators tended to decrease it.
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PMID:Modification of lymphocyte traffic by vasoactive neurotransmitter substances. 614 65

Calcium efflux from isolated rat parotid acinar cells was studied with 45Ca. Carbachol, phenylephrine, substance P, monobutyryl cyclic AMP and isoproterenol stimulated 45Ca efflux. It is suggested that carbachol, phenylephrine and substance P mobilize the same pool of cellular Ca. This suggestion is based on two observations. Firstly, combinations of any two of these three agonists at saturating concentrations result in no more 45Ca efflux than either agonist alone. Secondly, stimulation of 45Ca efflux by any one of the three agonists prevents further stimulation of 45Ca efflux by the same or one of the other two agonists. The pool of calcium mobilized by isoproterenol or monobutyryl cyclic AMP is different from the pool mobilized by carbachol. This conclusion is based on the observation that stimulation of 45Ca efflux by a saturating concentration of carbachol did not inhibit stimulation of 45Ca efflux by isoproterenol. Furthermore the effect of a saturating concentration of isoproterenol on 45Ca efflux is additive with that caused by a saturating concentration of carbachol. The effect of carbachol, phenylephrine and substance P on 45Ca2+ efflux did not require extracellular Ca2+.
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PMID:Regulation of calcium efflux from isolated rat parotid cells. 615 45


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