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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(+/-) Tiropramide hydrochloride, its D and L optical isomers and some of its metabolites were characterized in a number of in vitro pharmacological tests. Tiropramide showed broad spectrum antispasmodic activities on the isolated stomach of guinea pig electrically stimulated; on the longitudinal muscles of the ileum of guinea pig stimulated by electrical impulses, BaCl2, acetylcholine, histamine, serotonin, substance P and cholecystokinin octapeptide (CCK-8); on the spontaneous contractions and on the electrical inhibition of the jejunum of rabbit; on the spontaneous contractions and on the contractions provoked by BaCl2 and acetylcholine of the ascending colon of the rat; on the contractions provoked by BaCl2, acetylcholine, histamine and cerulein of the circular muscles of the gall bladder of the guinea pig; on the spontaneous contractions of the pyel-ureter preparation of the guinea pig; on the contractions of the uterus of the rat provoked by oxitocin, serotonin, acetylcholine, PGF2; on the spontaneous contraction of the portal vein of the rat; on the constriction of the tail artery of the rat provoked by electrical stimulation, epinephrine and ergotamine; on the contractions of the aortic strip of the rabbit stimulated by norepinephrine; on the contractions of the strip of bovine coronary artery depolarized by HCl. In general tiropramide had antispasmodic effect at 5-60 mumol/l concentration. It was more potent than papaverine on contractions provoked by electrical or chemical stimuli, and was less potent or ineffective on spontaneous and "physiological" contractions of the different smooth muscle preparations. Tiropramide had small effects on vascular smooth muscles and showed very small calcium channel blocking activity.
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PMID:Pharmacological characterisation of the smooth muscle antispasmodic agent tiropramide. 259 Feb 61

D,L-4-(3,4-Dichloro-benzoylamino)-5-(N-3-methoxypropyl- pentylamino)-5-oxo-pentanoic acid (CR 1505) belongs to a newly discovered class of agents with cholecystokinin (CCK) antagonistic activity. CR 1505 displaces CCK-8 from the central CCK receptors at concentrations of 9.1 mumol/l, and from the peripheral CCK receptors at concentrations of 0.33 mumol/l. CR 1505 antagonizes in vitro the contractant effects of CCK-8 on gall bladder strips of the guinea pig at 0.79 mumol/l and those on the small intestine at 1.6 mumol/l. These antagonistic effects are dose dependent and of competitive type. The antagonistic activities of CR 1505 against contractions of smooth muscles elicited by CCK-8 are at least 1000 times more potent than those against the contractions elicited by acetylcholine, BaCl2, histamine, serotonin, Substance P, bradykinin or dimethylphenylpiperazine. CR 1505 is also practically ineffective against the contractions of the small intestine of the guinea pig elicited by electrical field stimulations either as "cholinergic twich" (0.05 Hz), or as "cholinergic contractions" (trains of 10 min at 1 Hz), or as "non-cholinergic contractions" (200 impulses at 5 Hz in presence of atropine). CR 1505 is therefore a potent, specific, competitive and reversible CCK antagonist.
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PMID:Pharmacological characterisation of a new potent and specific nonpolypeptidic cholecystokinin antagonist. 366 68

Early studies indicated that the baCl2-induced contractions in the guinea pig ileum longitudinal muscle strip (GPI-LMS) were, in part, neuronal in origin. However, recent studies have suggested that BaCl2-induced contractions were produced by an action directly on the smooth muscle membrane. The purpose of this study was to investigate the mechanism of the BaCl2 contractions in the GPI-LMS. Botulinum toxin (5 x 10(5) MLD/mL), which blocks the electrically induced release of acetylcholine (ACh), hemicholinium-3 (HC-3; 110 micro M), which blocks ACh synthesis, tetrodotoxin (TTX; 60 nM), which blocks Na+ channels, black widow spider venom, which depletes the presynaptic neuron of neurotransmitter, and atropine (2.9 micro M), a potent muscarinic antagonist, had no effect on the BaCl2 contractions. Densensitization of the GPI-LMS to substance P did not affect the BaCl2 contraction. In Ca2+ -free buffer the BaCl2 dose-response curve was shifted to the right. In Ca2+-free solution the time to 50% inhibiton of the contractile response to ACh (73 nM) and BaCl2 (1.16 mM) was 3.7 and 125 min, respectively. The D 600 Ic50 for ACh and BaCl2 contractions was 220 and 130 nM, respectively. In Ca2+-free buffer either EGTA (0.53 mM) or D 600 (1 micro M) were potent inhibitors of BaCl2 contractions. These results suggest that in the GPI-LMS the BaCl2 response is not mediated by a release of ACh (or substance P) because inhibitors of ACh release, synthesis, and receptors do not affect the responses. Also, the BaCl2 contraction is not due to activation of Na+ channels because TTX is without effect. The BaCl2-induced contraction appears to be mainly due to the movement of membrane bound Ca2+ through D 600 sensitive Ca2+ channels with extracellular Ca2+ and possible passage of Ba2+ ions intracellularly playing relatively minor roles.
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PMID:BaCl2-induced contractions in the guinea pig ileum longitudinal muscle: role of presynaptic release of neurotransmitters and Ca2+ translocation in the postsynaptic membrane. 729 70

The effects of substance P (SP) and the selective NK1 receptor agonist [Sar9Met(O2)11] substance P on neonate rat spinal motoneurones were examined using intracellular recordings. Bath-administration of SP (0.1-3 microM) or [Sar9Met(O2)11] substance P (0.01-3 microM) induced a tetrodotoxin (TTX)-insensitive (10 microM) depolarization and a tetraethylammoniumchloride (TEA)-sensitive (3 mM) decrease in membrane conductance. The duration of the slow afterhyperpolarizations (AHPs) following the action potentials were significantly reduced (p = 0.003) by both NK1 receptor agonists. The mean duration of the sAHPs (+/- SEM) in control was 67.8 +/- 6.3 ms whereas in the presence of SP and [Sar9Met(O2)11] substance P their duration was reduced to 41.7 +/- 4.6 ms. Low Ca2+ (0.2 mM)-containing artificial cerebrospinal fluid (ACSF) or addition of BaCl2 or CdCl2 (2 mM) reduced the durations of the slow AHPs by 55%. In the presence of these agents SP and [Sar9Met(O2)11] substance P practically abolished the remaining slow AHPs, suggesting that the agonists also reduce a calcium-independent current. None of the effects induced by the NK1 receptor agonists were antagonized by the NK1 receptor antagonists (+/-)-CP-96,345 (10 microM), RP 67580 (1 microM) or GR 82334 (3-5 microM). In conclusion this study demonstrates that SP and [Sar9Met(O2)11] substance P elicit their effects on NK1 receptors by modulating at least two potassium currents, namely IK and ICa(K).
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PMID:The effects of neurokinin-1 receptor agonists on spinal motoneurones of the neonatal rat. 879 15

The rostral portion of the nucleus of the solitary tract (rNST) is an obligatory relay for gustatory afferent input on its way to the forebrain. Previous studies have demonstrated excitation of rNTS neurons by glutamate and substance P and inhibition by gamma-aminobutyric acid (GABA) and met-enkephalin (ENK). Despite the existence of cholinergic neurons and putative terminals within the rNTS, there are no data on the effects of acetylcholine (ACh) on rNTS processing. Here, we use patch-clamp recording of rNTS neurons in vitro to examine ACh-mediated responses and voltage-gated conductances in these cells. Results revealed (1) intrinsic voltage-gated inhibition via activation of voltage-gated potassium A-channels (I(A)), found almost exclusively in the medial rNTS, and hyperpolarization-activated potassium/sodium channels (I(h)), found more frequently in the lateral rNST; and (2) ligand-gated inhibition via activation of muscarinic m2 ACh receptors (mAChRs) linked to inward rectifier potassium channels (K(ir)) evenly distributed throughout the rNTS, a mechanism dependent on cholinergic inputs. Muscarinic responses were blocked by AFDX-116, a selective m2 mAChR antagonist, and by BaCl2, an antagonist of K(ir) channels. In addition, many rNTS neurons exhibited excitation via alpha7 and non-alpha7 nicotinic AChRs. Non-alpha7 nAChRs, blocked by 10 microM mecamylamine, occurred more frequently in the lateral rNTS. In contrast, alpha7 nAChRs, blocked by 20 nM methyllcaconitine, were evenly distributed across the nucleus. As previously reported for voltage-activated conductances, none of these currents was related to neuronal morphology. These voltage- and ligand-dependent inhibitory mechanisms would be expected to contribute to the modulation of gustatory processing through the NST.
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PMID:Cholinergic modulation of neurons in the gustatory region of the nucleus of the solitary tract. 1654 41