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)

Substance P is a vasoactive peptide. Nerve fibers containing substance P are present in the media of pulmonary arteries but the physiologic function of substance P in the pulmonary vasculature is unknown. Several doses of substance P were infused intravenously in the anesthetized dog to ascertain its effects on the pulmonary vasculature, both during normoxia and following preconstriction with hypoxia (F1O2 0.1) or prostaglandin F2 alpha (PGF2 alpha 5 mug/kg/min). Substance P resulted in systemic vasodilation during normoxia but had minimal effect on the pulmonary vasculature. During hypoxia and PGF2 alpha-induced pulmonary vasoconstriction, substance P significantly lowered pulmonary artery pressure, pulmonary vascular resistance, mean aortic pressure, and total systemic resistance. It had no effect on cardiac output, wedge pressure, and arterial blood gases. To investigate possible mechanisms for substance P-induced vasodilation, substance P was studied following pretreatment with N-acetylcysteine (a radical scavenging agent), methylene blue (an inhibitor of guanylate cyclase), meclofenamate (a cyclooxygenase inhibitor), and atropine (a muscarinic receptor antagonist). None of these agents impaired substance P-induced vasodilation. Substance P given intravenously is a nonselective vasodilator in the dog but the mechanism of its action remains uncertain.
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PMID:The effects of substance P on the preconstricted pulmonary vasculature of the anesthetized dog. 242 48

The effect of four neuropeptides and acetylcholine on the release of leukotrienes LTC4, LTD4 and LTE4 from platelet activating factor-stimulated rat lung and ionophore A23187-stimulated guinea pig lung, as detected by the combined use of HPLC and radioimmunoassay, was studied. Both vasoactive intestinal peptide and calcitonin gene-related peptide were found to inhibit the release of leukotrienes in both preparations. This effect was most marked in platelet activating factor-stimulated rat lung, where inhibition of LTC4 release was more pronounced than either inhibition of LTD4 or LTE4 production. The effect of vasoactive intestinal peptide on LTC4 biosynthesis was dose-related in rat lung. Neither substance P nor beta-endorphin were found to inhibit leukotriene release in rat lung. Vasoactive intestinal peptide inhibition of leukotriene release is independent from its actions on the muscarinic receptor, since acetylcholine was found to have no effect in the same preparation.
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PMID:The effect of vasoactive intestinal peptide and calcitonin gene-related peptide on peptidoleukotriene release from platelet activating factor stimulated rat lungs and ionophore stimulated guinea pig lungs. 243 97

Low doses of vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) have been shown to augment the salivary volume secretion evoked by muscarinic receptor agonists or substance P (SP) in rat parotid gland. Since VIP and CGRP are known to activate adenylate cyclase, we have studied whether forskolin, which directly activates this enzyme, can mimic the effects of these peptides on salivary secretion from the parotid gland in anaesthetized (Inactin 0.5 g kg-1 i.p.) rats. We have also studied the effect of the secretagogues and peptides on glandular blood flow as revealed by the laser Doppler technique. Carbachol (5 nmol kg-1) and SP (185 pmol kg-1) injected i.v. caused a transient increase in parotid blood flow and a decrease in systematic blood pressure concomitant with a salivary secretion of 3.3 +/- 0.3 mg (n = 22) and 18.7 +/- 1.9 mg (n = 25) respectively. VIP (150 pmol kg-1) and CGRP (25 pmol kg-1) also caused a transient increase in glandular blood flow concomitant with a decrease in systemic blood pressure, but no salivary secretion. The glandular blood flow increased by 166 +/- 5% and 43 +/- 11% for VIP and CGRP respectively. When carbachol was given 20 s after the injection of VIP or CGRP, the secretory response was increased by about 250% and 60% respectively. The adenylate cyclase stimulator forskolin (2.5 pmol kg-1) produced the same type of response regarding blood flow and systemic blood pressure as VIP and CGRP and potentiated the salivary secretion evoked by carbachol (5 nmol kg-1) by about 100%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The enhancement of carbachol-induced salivary secretion by VIP and CGRP in rat parotid gland is mimicked by forskolin. 248 55

The relationship between ion movements (sodium uptake and potassium release) and agonist-induced contractile responses or muscarinic receptor binding was investigated in the guinea pig ileal longitudinal muscle (GPLM). Sodium uptake and potassium release were agonist-dependent, concentration-dependent, and stereoselective, with the following rank order of maximum ion movement: muscarinic agonists greater than histamine greater than substance P = serotonin. Potassium depolarization did not initiate sodium uptake or potassium release. Sodium uptake was rapid and monophasic, preceding potassium release which was biphasic in nature. Full muscarinic agonists produced equal maximal increases in sodium uptake, while maximal potassium release varied for all muscarinic agonists and in addition differed from sodium uptake in the following ways: time course, stereoselectivity, sensitivity to calcium antagonists, modulation by the guanylyl nucleotide derivative, 5'-guanylylimidodiphosphate (Gpp(NH)p), and inhibition by muscarinic receptor blockade with benzilylcholine mustard. The calcium ionophores A23187 and ionomycin (SQ23377) did not produce any sodium uptake; A23187 but not ionomycin produced potassium release comparable to that evoked by muscarinic agonists. Ion movement in response to combinations of agonists were not additive. Muscarinic agonist binding as measured by competition for [3H]quinuclidinyl benzilate ([3H]QNB) binding, was best described by multiple sites and was regulated by Gpp(NH)p. Excellent correlations were observed between the dissociation constants for binding and sodium uptake, potassium release, and contraction. The best correlations were those between the pharmacologic responses and the high affinity binding site in the absence, and the low affinity site in the presence, of Gpp(NH)p, respectively. Furthermore, the potencies of muscarinic agonists to evoke ion movements and to inhibit [3H]QNB binding were similar, and from one to two orders of magnitude less than those for contraction. It is suggested that contraction and potassium release were mediated by the high affinity, and sodium uptake by the low and average affinity muscarinic agonist binding sites, respectively. These findings suggest an agonist-activated receptor-effector coupling model in GPLM that leads to the activation of sodium uptake, potassium release, and subsequently, contraction.
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PMID:Characterization of ion movements and their relationship to muscarinic receptor binding and excitation-contraction coupling in guinea pig ileal longitudinal smooth muscle. 275 75

Grafts of fetal striatum were implanted in the form of a cell suspension into the brains of rats with prior ibotenic acid lesions of the caudate-putamen. The grafts were placed in three different sites: the lesioned caudate-putamen, or the denervated (but otherwise undamaged) globus pallidus and substantia nigra. After 3-6 months survival the grafts were investigated by means of immunohistochemistry and receptor autoradiography in combination with routine histology and acetylcholinesterase histochemistry. The grafts placed within the lesioned caudate-putamen were at least 10-fold larger larger than those placed in the substantia nigra region, with the grafts placed in the globus pallidus being of intermediate size. In all locations the acetylcholinesterase staining had an uneven, patchy distribution, which was most pronounced in the grafts located within the caudate-putamen. These patches did not bear any obvious relationship to variations in density of the neuronal perikarya within the grafted tissue. Many of the neuropeptide-immunoreactive neuron types present in the normal striatum, such as those containing substance P, [Met]enkephalin, somatostatin, cholecystokinin and neuropeptide Y were also detected in the grafted striatum along with acetylcholinesterase-positive staining. Acetylcholinesterase-positive, [Met]enkephalin-positive, substance P-positive and tyrosine hydroxylase-positive markers all showed uneven, patchy distributions in the grafts. This was also the case for the distribution of dopamine D2 and opiate receptors (as revealed by [3H]spiroperidol and [3H]diprenorphine autoradiography, respectively), whereas muscarinic receptor binding was even throughout the grafts. As is the case in the so-called striosomal patches (neurochemically defined compartments) in the immature intact striatum during the early postnatal period, patches of high acetylcholinesterase staining in the grafts showed partial correspondence with patches of high [Met]enkephalin fibre staining, and dopamine receptor density, and (although to a lesser degree) also with patches of high opiate receptor density and high substance P-immunoreactivity. This correspondence of patches also occurred between tyrosine hydroxylase fibre staining and acetylcholinesterase staining as revealed by grafts placed into the substantia nigra. These results suggest that the fetal striatal cell suspension grafts will give rise to a fairly normal range of striatal neuron and receptor types and that they develop at least some of the striosomal features characteristic for the normal striatum.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neural grafting in a rat model of Huntington's disease: striosomal-like organization of striatal grafts as revealed by acetylcholinesterase histochemistry, immunocytochemistry and receptor autoradiography. 282 74

Parkinson's disease is characterized by a deficiency of dopamine in the nigrostriatal system. However, changes in dopamine neurons were found also outside the extrapyramidal system, showing that there is a more general brain defect than just the loss of substantia nigra dopamine neurons. With regard to the behavior of striatal D-2 receptors it was possible to divide parkinsonian patients into two subgroups, because either a decrease or an increase in the number of D-2 receptors was found. Clinically, the patients with a decreased number of striatal D-2 receptors were more disabled and had lost the beneficial response to levodopa. D-3 receptor binding sites were decreased in the parkinsonian striatum. Changes in the cholinergic-muscarinic receptors in the striatum seem to be related to changes in D-2 receptors, and muscarinic receptor supersensitivity was found in cortical areas. GABA receptor binding was decreased in the substantia nigra. In the parkinsonian brain there seems to be supersensitivity of a population of enkephalin receptors (delta) in the striatum and in the limbic system and also a loss of others (mu) in the striatum. Furthermore, the Met-enkephalin content was decreased in the parkinsonian substantia nigra. A decreased concentration of substance P was found in the substantia nigra of all parkinsonian patients and in the putamen of those patients who had not received levodopa treatment. The somatostatin level was decreased in the frontal cortex in relation to dementia. There are thus multiple neuronal disturbances in the parkinsonian brain, although those of the nigrostriatal dopamine neurons seem to be the greatest and are more closely related to parkinsonian clinical features and to treatment responses.
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PMID:Brain neurotransmitters and neuropeptides in Parkinson's disease. 609 88

Repetitive preganglionic nerve stimulation increases cyclic guanosine 3':5'-monophosphate (cGMP) content in rat superior cervical ganglia by a mechanism requiring Ca++ but resistant to blockade by cholinergic receptor antagonists. Similarly, 45Ca-uptake during prolonged preganglionic nerve stimulation is unaffected by hexamethonium or atropine. These findings indicate that nerve stimulation increases cGMP accumulation and 45Ca-uptake by a noncholinergic mechanism Substance P, met-enkephalin and luteinizing hormone-releasing factor have little or no effect on cGMP content. By contrast, bethanechol causes a 3-fold increase in cGMP content and postganglionic cell firing. Thus, as reported by others, muscarinic receptor activation increases ganglionic cGMP[. 4-Aminopyridine causes an increase in cGMP of resting ganglia that requires Ca++ and the nerve terminal is blocked by tetrodotoxin but unaffected by atropine or hexamethonium. Ouabain also increases ganglionic cGMP content by a process that requires Ca++ and the nerve terminals. Like preganglionic nerve stimulation, 4-aminopyridine and ouabain cause cGMP accumulation in the nerve terminals or in the ganglion cells as a consequence of releasing a noncholinergic transmitter. The uptake of Ca++ by ganglion cells is not an adequate stimulus for cGMP accumulation because the nicotinic receptor agonist dimethylphenylpiperazinium increases 45Ca-uptake but has no effect on cGMP formation in ganglia.
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PMID:Cyclic guanosine 3':5'-monophosphate accumulation and 45Ca-uptake by rat superior cervical ganglia during preganglionic stimulation. 611 99

The inhibitory effect of atropine on phospholipid 32P labelling stimulated by muscarinic or alpha-adrenergic agonists was studied in isolated parotid cells. Atropine (10(-11) to 10(-4) M) had no effect on phospholipid 32P labelling in unstimulated cells. In contrast, 10(-8) to 10(-7) M atropine provoked a competitive inhibition of the cholinergic stimulation (i.e. this effect was completely wiped out at high agonist concentration). The atropine app. KD for the muscarinic receptor was 5 X 10(-9) M. Moreover, atropine inhibits the adrenergic stimulation of phospholipid 32P labelling by decreasing the efficacity and potency of the adrenergic agonists. The atropine app. KD for the alpha-adrenergic receptor can be estimated at 10(-5) M. This inhibition of alpha-adrenergic stimulation appears to be specific since atropine was without effect on the substance P or beta-adrenergic stimulation. At very low concentration (10(-10) - 10(-9) M) atropine seems to be a modulator (activator) of the muscarinic or adrenergic agonist-receptor complex. From the present data, it is suggested that atropine, besides its classical blocker effect at the muscarinic receptor, at high concentration is a specific alpha-adrenergic antagonist.
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PMID:Comparative effect of atropine on the adrenergic and muscarinic stimulation of phospholipid 32P labelling in isolated parotid cells: atropine, a possible blocker of alpha-adrenergic receptors. 632 Sep 38

The effects of carbachol on uptake of 22Na by enzymatically dispersed rat pancreatic acinar cells were determined. Carbachol caused a slight but significant increase in uptake of 22Na by the cells in the presence of absence of ouabain (10(-3) M). A maximal response was obtained with 10(-6) M carbachol. The effects of carbachol were blocked by 10(-5) M atropine. Caerulein (10(-7) M) also stimulated 22Na uptake, while epinephrine (10(-4) M) and substance P (10(-7) M) did not. Carbachol did not stimulate 22Na uptake in the absence of extracellular Ca, although Ca omission significantly elevated basal 22Na uptake. The divalent cationophore A-23187 caused Ca-dependent 22Na uptake at 20 microM concentration but not at 0.3 microM. These results, when considered with earlier reports by others, suggest that muscarinic receptor activation leads to an increase in permeability of the acinar cell membrane to Na, and that Ca may be second messenger for this effect.
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PMID:Effect of carbachol on radiosodium uptake by dispersed pancreatic acinar cells. 719 Feb 70

N omega-Nitro-L-arginine methyl ester has been reported to have muscarinic receptor blocking activity whereas the nonesterified analog does not bind to muscarinic receptors. The present study was, therefore, undertaken to compare the inhibitory effects of N omega-nitro-L-arginine methyl ester with those of N omega-nitro-L-arginine on baseline tone and on vasodilator responses to acetylcholine, bradykinin, and substance P in the mesenteric vascular bed of the cat under constant flow conditions. Administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine in doses of 100 mg/kg i.v. increased baseline tone in the mesenteric vascular bed and inhibited mesenteric vasodilator responses to acetylcholine, bradykinin, and substance P. The increase in mesenteric arterial perfusion pressure and the decrease in vasodilator responses to the three endothelium-dependent vasodilator agents following administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine did not differ significantly. The nitric oxide synthase inhibitors did not attenuate vasodilator responses to agents that induce vasodilation by nonendothelium-dependent mechanisms and enhanced responses to the nitrovasodilators. Atropine blocked vasodilator responses to acetylcholine but did not alter responses to bradykinin or substance P. The similarity in the inhibitory effects of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine on responses to acetylcholine, bradykinin, and substance P suggest that the L-arginine analog, N omega-nitro-L-arginine, as well as the methyl ester of N omega-nitro-L-arginine, are useful probes for studying endothelium-dependent vasodilator responses in the mesenteric vascular bed of the cat.
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PMID:Comparative effects of N omega-nitro-L-arginine and N omega-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, bradykinin, and substance P. 751 84


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