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)

Dimaprit, a highly selective H2-agonist, caused a multiphasic contraction of guinea-pig ileal segments and ileal myenteric plexus-longitudinal muscle preparations. The initial phase was characterized by a twitch which reached a maximum in 15 to 30 sec and was followed by a partial relaxation. The later phase was variable and consisted of a series of twitch responses or of a slowly developing contracture which sometimes was accompanied by oscillatory changes in tension. dose-response curves were generated for the initial response; for isolated ileal segments the EC50 was 5.1 +/- 1.8 micrometers (mean +/- S.D., N = 7) and the Hill coefficient was 1.1 +/- 0.2 and for longitudinal muscle strips the EC50 was 5.8 +/- 1.2 micrometer and the Hill coefficient was 1.2 +/- 0.1 (N = 7). Both the initial and secondary components of the contractile responses to dimaprit were prevented by 0.2 micron tetrodotoxin or 10 microns mefenamic acid and by the production of tachphylaxis to either substance P or serotonin. Scopolamine, 0.001 to 0.1 micron, insurmountably antagonized only the initial component of the response. Mepyramine (1.0 micrometer), hexamethonium (100 microns), bromolysergic acid (0.25 microns) and p-(imidazol-1-yl)phenyl (10 microns) were without effect on the response to dimaprit. The histamine H2-receptor antagonist, tiotidine, produced parallel dextral shifts in the dose-response curve for dimaprit. The apparent pA2 value for tiotidine was 7.65. The results suggest that dimaprit acts on H2-receptors located on myenteric plexus neurons to cause the release of contractile substances. The mediators of the contractile response are tentatively identified as acetylcholine, substance P, serotonin and a product(s) of the arachadonic acid cascade.
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PMID:Histamine H2-receptors on guinea-pig ileum myenteric plexus neurons mediate the release of contractile agents. 617 31

We investigated the effects of intracerebroventricular injection of substance P (SP) on the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance in the mouse. SP (0.001-3 micrograms) alone did not influence either spontaneous alternation performance or total arm entries. Scopolamine (1 mg/kg) impaired spontaneous alternation performance accompanied by an increment in total arm entries. In contrast, SP (0.01-1 micrograms) significantly improved the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without influencing the scopolamine (1 mg/kg)-induced increase in total arm entries. The effects of SP (0.1 micrograms) on the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance were almost completely reversed by pretreatment with WIN 62577 (1 mg/kg), a tachykinin NK-1 receptor antagonist. These results suggest that SP improves the scopolamine-induced impairment of spontaneous alternation performance through the mediation of tachykinin NK-1 receptors.
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PMID:Substance P markedly ameliorates scopolamine-induced impairment of spontaneous alternation performance in the mouse. 754 97

Ninety-five percent of the neurons in the corpus striatum of the rat are medium spiny projection neurons, which contain tachykinins such as substance P, neurokinin A, and neurokinin B and the opiate peptides, enkephalin and dynorphin. The remaining 5% consist of interneurons, of which a small but significant proportion are cholinergic. The influence of these cholinergic interneurons on the neuropeptidergic projection systems in the striatum is poorly understood at this time. The present study explores the relationship between cholinergic receptor activation or muscarinic blockade on striatal neuropeptide gene expression. Adult male Sprague-Dawley rats were treated chronically either with a cholinergic agonist (physostigmine: 0.5 mg/kg/3 x day), a muscarinic antagonist (scopolamine HCl: 0.4 mg/kg/3 x day), or vehicle (PBS: 0.1 ml/100 g) administered for 6 days (s.c.). In situ hybridization was performed with probes directed against mRNAs for beta-preprotachykinin (a transcript containing substance P, neurokinin A, and other tachykinins), neurokinin B and preproenkephalin. Physostigmine administration resulted in a 12% decrease in the dorsolateral caudate-putamen and a 27% increase in the core of the nucleus accumbens in substance P/neurokinin A mRNA; and a 29% increase in the caudate-putamen and an 11% increase in the core of the nucleus accumbens in preproenkephalin mRNA levels. Scopolamine treatment resulted in a 28% and 48% decrease, respectively, in the caudate-putamen and in the shell of the nucleus accumbens in substance P/neurokinin A mRNA levels. Neurokinin B mRNA levels were increased by 50% in the shell of the accumbens after scopolamine. Preproenkephalin mRNA levels increased by 24% in the caudate-putamen and decreased by 20% in the core of the nucleus accumbens. From these results we tentatively conclude that cholinoceptive neuropeptidergic neurons are segregated along dorsoventral and mediolateral axes in the striatum, thus giving rise to non-homogenous responses upon cholinergic receptor activation or muscarinic blockade.
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PMID:Cholinergic regulation of tachykinin- and enkephalin-gene expression in the rat striatum. 763 70

Cholinergic neurons play a major role in the control of striatal activity via muscarinic receptors. The action of acetylcholine also appears to be dependent on the striosome-matrix compartmentalization of the striatum. This study was designed to find out whether modification of acetylcholine tone activates neurons in the striatum and forebrain of the rat. We looked for the appearance of immunoreactivity to Fos, a regulatory protein that is thought to convert synaptic signals into changes in gene expression. Pharmacological manipulation of muscarinic receptors was found to induce specific patterns of Fos immunoreactivity in distinct neuronal populations of the forebrain, including the striatum. Oxotremorine, a non-selective muscarinic agonist, induced Fos immunoreactivity in the striatum with a large predominance in striosomes (mostly in enkephalinergic neurons), in layers 4 and 6 of the cortex, and also in the piriform cortex and septum. The muscarinic agonist pilocarpine had an identical effect in the cortex, but the striosomal prevalence was less clear-cut than that observed after oxotremorine. Treatment with dopamine-depleting agents (6-hydroxydopamine or reserpine) and inhibitors of glutamate and opiate receptor (MK-801 and naloxone respectively) had no effect on the action of oxotremorine. This suggests that the induction of Fos provoked by oxotremorine does not involve dopamine, glutamate or opiates. Atropine, a non-specific muscarinic antagonist, also induced Fos immunoreactivity in the striatum but with matrix predominance (mostly in substance P neurons), as well as in the cingulate cortex, and the olfactory tubercle. Scopolamine, a muscarinic antagonist, induced Fos in both striosomal and matrix compartments in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fos immunoreactivity after stimulation or inhibition of muscarinic receptors indicates anatomical specificity for cholinergic control of striatal efferent neurons and cortical neurons in the rat. 828 24

The involvement of dopamine receptors in the beneficial effects of intracerebroventricular injection of substance P, neurokinin A and senktide on the scopolamine-induced impairment of spontaneous alternation performance was investigated in mice. Scopolamine (1 mg/kg) significantly impaired spontaneous alternation performance, while substance P (0.1 microg), neurokinin A (0.3 microg), senktide (0.003 microg) and S(-)-sulpiride (10 mg/kg), a dopamine D2 receptor antagonist, improved the scopolamine (1 mg/kg)-induced disturbance of spontaneous alternation performance. However, the dopamine D1 receptor antagonist SCH23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine maleate) did not influence the scopolamine-induced disturbance of spontaneous alternation performance. The dopamine D2 receptor agonist RU24213 (N-n-propyl-N-phenylethyl-p-(3-hydroxyphenyl)-ethylamine hydrochloride) (1 mg/kg) but not the dopamine D1 receptor agonist SKF38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepine hydrochloride) (3 and 10 mg/kg) reversed the beneficial effects of substance P (0.1 microg) and neurokinin A (0.3 microg) on the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. In contrast, neither SKF38393 (3 and 10 mg/kg) nor RU24213 (0.3 and 1 mg/kg) significantly affected the beneficial effects of senktide (0.003 microg) on the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. Although RU24213 (1 mg/kg) and SCH23390 (0.03 mg/kg) markedly decreased total arm entries, SKF38393 (10 mg/kg), RU24213 (1 mg/kg), SCH23390 (0.03 mg/kg) or S(-)-sulpiride (10 mg/kg) had no significant effects on spontaneous alternation performance. These results suggest that stimulation of dopamine D2 but not D1 receptors reverses the ameliorative effects of substance P and neurokinin A, whereas neither dopamine D1 nor D2 receptors play an important role in the beneficial effects of senktide on the scopolamine-induced impairment of spontaneous alternation performance associated with spatial working memory.
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PMID:Involvement of dopamine receptors in beneficial effects of tachykinins on scopolamine-induced impairment of alternation performance in mice. 968 12

A circular and a longitudinal muscle strip were prepared from adjacent parts of a guinea-pig ileum and a direct pharmacological comparison made under identical conditions. The longitudinal preparation was sensitive to acetylcholine, methacholine, carbachol, 5-hydroxytryptamine, histamine and nicotine, while the circular preparation was insensitive to 5-hydroxytryptamine, histamine and nicotine, and responded to the choline esters only in high concentrations. Incubation of the preparations with the anticholinesterase, mipafox (NN-diisopropylphosphodiamidic fluoride), sensitized both preparations to the action of acetylcholine; potentiation of the contraction of the longitudinal muscle was 16-times; that of the circular one 4,000-times. The longitudinal muscle was more sensitive than the circular muscle to acetylcholine whether both were treated with mipafox or not. Bradykinin and substance P both stimulated the longitudinal but not the circular muscle, an effect not modified after mipafox. Hyoscine antagonized the responses of the circular muscle strip, treated with mipafox, to acetylcholine and to histamine, but on the longitudinal muscle strip the response to histamine was not affected, the response to acetylcholine being competitively antagonized. Morphine, in the same concentrations on both circular and longitudinal muscle strips, antagonized the stimulant actions of nicotine and to a lesser extent of 5-hydroxytryptamine, but the responses to histamine on the longitudinal muscle strip were not antagonized by morphine which was in contrast to its action on the circular muscle strip. These observations showed that the main differences in the responses of the circular and longitudinal muscle of the guinea-pig ileum to drugs were in the intrinsic properties of the smooth muscle cells. In addition cholinesterase may protect the circular muscle cells. Finally the circular muscle strip preparation proved to be a useful tool to study the action of drugs on the nervous plexuses of the ileum of the guinea-pig.
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PMID:SOME PHARMACOLOGICAL PROPERTIES OF THE CIRCULAR AND LONGITUDINAL MUSCLE STRIPS FROM THE GUINEA-PIG ISOLATED ILEUM. 1411 Jul 54

Tachykinins (TKs) colocalize with acetylcholine in excitatory motor neurones supplying human colonic circular muscle (CCM). Some children with slow-transit constipation (STC) have reduced TK-immunoreactivity in nerve terminals in CCM suggesting a deficit in neuromuscular transmission. This study aimed to test this possibility. Seromuscular biopsies of transverse colon were obtained laparoscopically from STC children (37, 17 with low density of TK-immunoreactivity). Specimens of transverse (17) and sigmoid colon (20) were obtained from adults undergoing colonic resection for cancer. CCM contractions were measured isotonically and responses to carbachol, neurokinin A (NKA) and electrical field stimulation (EFS) recorded. Carbachol and NKA-evoked contractions in adult and STC colon. Hyoscine (2 micromol L-1) significantly depressed responses to EFS in all preparations. Blockade of NK2 receptors (SR 48968, 2 micromol L-1) significantly depressed EFS-evoked contractions of adult transverse CCM, but had no effect on STC preparations. Thus, neuromuscular transmission in both adults and STC children is predominantly cholinergic and this component is unimpaired in the latter, indicating that reduced TK-immunoreactivity is not a marker for depressed cholinergic responses. Although pharmacologically responsive TK receptors are present in STC colon, we did not detect neuromuscular transmission mediated by release of TKs in these preparations.
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PMID:Cholinergic transmission to colonic circular muscle of children with slow-transit constipation is unimpaired, but transmission via NK2 receptors is lacking. 1465 3