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 and calcitonin gene-related peptide were immunohistochemically identified in axons innervating the cornea and the ureter of adult rats and pigeons. The two neuropeptides were similarly distributed in both species. Capsaicin pretreatment induced depletion of the immunoreactivity; this was quantitatively and qualitatively different in rats and pigeons. Topical application of capsaicin (1%) reduced the immunoreactivity in the cornea in both species by 50%. Systemic capsaicin treatment completely depleted both peptides from the corneal innervation of rats but reduced the peptide content only by 50% in the cornea of pigeons. In the ureter of rats, capsaicin pretreatment completely depleted the peptide immunoreactivity. In pigeons the peptide depletion was only complete in the outer longitudinal muscle layer. Whereas only a few immunoreactive fibres were observed in the circular muscle layer, about 50% of the peptide remained in the inner longitudinal muscle layer. The results demonstrate that peptidergic afferents in the cornea and ureter of pigeons are sensitive to capsaicin, although birds do not show nociceptive responses to local administration of the drug. The long-term depletion of substance P and calcitonin gene-related peptide by capsaicin is discussed with regard to the possibility that functionally capsaicin receptors may exist in the axon but not at nerve endings.
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PMID:Effects of capsaicin in rat and pigeon on peripheral nerves containing substance P and calcitonin gene-related peptide. 247 91

(+/-) 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

Either intra-arterial or topical administration of calcitonin gene-related peptide (CGRP) had little effect on motility of the urinary bladder in urethane-anaesthetized rats. Only a high concentration (50 microM) of topical CGRP activated the micturition reflex and potentiated the response to exogenous substance P (SP). In the isolated rat bladder CGRP had inconsistent effects on spontaneous or field-stimulated contractions. CGRP neither produced any significant plasma extravasation (Evans blue leakage) in the rat lower urinary tract, nor potentiated the response to exogenous SP. CGRP inhibited motility in the rat isolated proximal urethra and ureters and counteracted the contractile response to neurokinins. An inhibitory effect of capsaicin on stimulated motility of the urethra was observed in all preparations and a small contractile response was evident in about 40% of cases. Lack of desensitization to the action of CGRP prevented the study of its interaction with capsaicin. The inhibitory effect of CGRP in the ureter exhibited a specific desensitization: if the preparations were pre-exposed to exogenous CGRP, the inhibition of motility produced by antidromic activation of the capsaicin-sensitive nerve terminals (field stimulation) as well as the response to capsaicin (1 microM) was prevented but the inhibitory response to isoprenaline was unaffected. These findings indicate that CGRP is able to influence markedly the motility of the rat lower urinary tract, but exhibits marked regional differences in its action. Endogenous CGRP could be the inhibitory transmitter which, when released from capsaicin-sensitive fibers, participate in the control of ureteral motility.
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PMID:Visceromotor responses to calcitonin gene-related peptide (CGRP) in the rat lower urinary tract: evidence for a transmitter role in the capsaicin-sensitive nerves of the ureter. 282 87

Muscle strips from the fundus, trigonum and distal ureters obtained from children at operations for vesico-ureteric reflux were studied using histochemical and immunohistochemical methods, and electrical nerve stimulation in an organ bath. A rich supply of cholinergic nerves was found and despite a partial atropine resistance the neurophysiological experiments indicated that the transmitter causing contraction of the detrusor muscle is acetylcholine. Imipramine, which is used in the treatment of enuresis, had no anticholinergic effect on the bladder in the doses used clinically. The adrenergic innervation was very sparse except around the ureter orifices. No contractile alpha-adrenoceptors could be detected but beta receptor mediated relaxation was found, which was neither of the beta 1 nor beta 2 type. A third type of beta receptor is postulated. Peptidergic nerves containing vasoactive intestinal peptide, VIP, were demonstrated in a few nerve terminals running along bundles of smooth muscle. No nerves containing enkephaline, somatostatine or substance P were found. VIP affected the detrusor muscle indicating a possible role as a modulator of transmitter action, while substance P had no effect. The anticholinergic and calcium antagonistic drug terodiline inhibited all muscle activity, whether it was induced by nerve stimulation, cholinergic drugs or a potassium rich solution, making it suitable for treatment of diurnal enuresis.
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PMID:Innervation of the child urinary bladder. 302 85

1. Comparison of the tissue content of calcitonin gene-related peptide (CGRP)-immunoreactivity (IR) and tachykinin (TK)-IR in the rat and guinea-pig ureter showed that in the rat tissue levels of CGRP-IR were 33-fold higher than those of TK-IR. In the guinea-pig ureter, both peptides were present in nearly the same concentration. 2. The in-vitro release of neuropeptides from guinea-pig and rat ureters was investigated using capsaicin as a stimulus for afferent neurons. Capsaicin induced the simultaneous release of CGRP-IR and TK-IR from the guinea-pig ureter while in the rat only the release of CGRP-IR was detectable. 3. It is known that TK potently stimulate and CGRP inhibits ureteric smooth muscle contractions. When the effect of capsaicin on ureteric motility was investigated in guinea-pig and rat, only in the guinea-pig ureter a stimulatory action ascribable to capsaicin-induced TK release was observed thus supplementing the results obtained by radioimmunoassay. 4. The results show that considerable species differences exist concerning the ratio of CGRP and TK which is stored and released from ureteric afferent nerve terminals. As a consequence, different functional responses are obtained in both species upon stimulation of these neurons by capsaicin. In the rat ureter, the capsaicin-sensitive innervation seems to be only inhibitory while in the guinea-pig stimulatory and inhibitory transmitters are released. The physiological significance of the simultaneous release of transmitters with opposing effects needs further investigation.
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PMID:Species-related differences in the capsaicin-sensitive innervation of the rat and guinea-pig ureter. 326 56

Tachykinin- and calcitonin gene-related peptide (CGRP) immunoreactivities were localized by immunohistochemistry in the same nerves of the kidney, renal pelvis and ureter as well as in spinal ganglion cells of both the guinea-pig and man. The tachykinin and CGRP-immunoreactive nerves in the ureter were present within the smooth muscle layers, around blood vessels, close to and within the lining epithelium. The levels of neurokinin A-, substance P- and CGRP-like immunoreactivity per tissue weight, as determined by radioimmunoassay, were about 30-100-fold higher in the guinea-pig than in the human ureter, which was in good agreement with the relative density of immunoreactive nerve fibres, as seen by immunohistochemistry. Capsaicin treatment caused an almost total disappearance of both neurokinin A-, substance P- and CGRP-immunoreactive nerve fibres in the guinea-pig ureter and a 90% depletion of neurokinin A, substance P- and CGRP-like immunoreactivity, further supporting a sensory origin of these nerves. Reversed-phase high performance liquid chromatography of water extracts of the human ureter revealed the presence of neurokinin A- and eledoisin-like material using antiserum K12, which does not cross-react with substance P. Most of the CGRP-like immunoreactivity in human ureter extracts co-eluted with synthetic human CGRP. Capsaicin both caused inhibition of spontaneous motility of the human ureter in vitro and initiated contractions in some preparations. Neurokinin A and neuropeptide K potently initiated phasic contractions of the ureter, while substance P had only minor contractile effects. CGRP inhibited both spontaneous and neurokinin A-induced ureteric contractions. In conclusion, peptides with potent opposite motility effects are present in the same, presumably sensory nerves of the ureter in both the guinea-pig and man. It will be of importance to determine whether local release of neuropeptides can account for ureteric motility changes accompanying sensory nerve activation upon ureteral obstruction, by e.g. renal calculi.
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PMID:Co-localization of tachykinins and calcitonin gene-related peptide in capsaicin-sensitive afferents in relation to motility effects on the human ureter in vitro. 350 48

Muscle strips from the fundus, trigone, and distal ureter obtained from children at operation for vesicoureteric reflux were studied using histochemical and immunohistochemical methods, and electrical nerve stimulation in an organ bath. A rich supply of cholinergic nerves was found and the transmitter causing contraction of the detrusor muscle was regarded as being acetylcholine. The adrenergic innervation was very sparse except around the ureteric orifices. No contractile alpha-adrenoceptors could be detected but beta-receptor-mediated relaxation was found. The type was not beta 1 or beta 2, suggesting a third type of beta-receptor. Peptidergic nerves containing vasoactive intestinal peptide (VIP) were demonstrated in a few nerve terminals. No nerves containing enkephalin, somatostatin, or substance P were found. VIP affected the detrusor muscle, indicating a possible role as a modulator of transmitter action. Imipramine, used for enuresis, had no anticholinergic effect on the bladder in the doses used clinically. The anticholinergic and calcium antagonistic drug terodiline inhibited all muscle activity, making it suitable for treatment of diurnal enuresis.
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PMID:Urinary bladder innervation in children. 355 68

Intravenous injection of compound 48/80 (1 mg X kg-1) induced an acute increase in vascular permeability to plasma proteins in various organs of rats. The compound 48/80 response was partly inhibited by histamine H1 and H2 receptor blockade in the urinary bladder and in the duodenum, but not in the trachea, the oesophagus, the ureter and the paw skin. Blockade of 5-hydroxytryptamine receptors with methysergide led to a reduction of the permeability response in the oesophagus and in the urinary bladder, leaving responses in other organs unchanged. Pretreatment of neonatal rats with capsaicin almost abolished the 48/80 response in all organs except in the duodenum. Pretreatment of rats with [D-Arg1, D-Trp7,9, Leu11]-substance P, a substance P antagonist, also caused a partial inhibition of the permeability response to compound 48/80 in several organs. Topical administration of compound 48/80 (1 mg X ml-1) onto the tracheal mucosa induced local Evans blue extravasation. This response was resistant to pretreatment with histamine receptor antagonists, but was largely inhibited after neonatal capsaicin pretreatment. Topical administration of compound 48/80 (1 mg X ml-1 or 10 mg X ml-1) into the eye did not cause visible Evans blue extravasation in the conjunctiva, nor any signs of pain reaction as indicated by the absence of the wiping response, usually seen upon noxious chemical stimuli in the eye. In guinea-pigs, 10 mg X kg-1 compound 48/80 i.v. were required to induce vascular protein leakage in different organs. This response was blocked by pretreatment with H1 and H2 receptor antagonists, but only slightly reduced after systemic capsaicin pretreatment of guinea-pigs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of compound 48/80--induced vascular protein leakage by pretreatment with capsaicin and a substance P antagonist. 608 60

The effects of substance P (SP), substance K (SK), physalaemin, eledoisin, kassinin, neuromedin K and bombesin on blood pressure, heart rate, respiratory insufflation pressure and plasma extravasation were studied in the guinea-pig. All tachykinins except neuromedin K caused a fall in blood pressure with rather similar potency. The hypotensive response after physalaemin was comparatively more long-lasting. SK and eledoisin (2.5 nmol X kg-1 i.v.) caused an initial bradycardia which then changed into tachycardia. The other tachykinins induced a slowly developing tachycardia. Neuromedin K (up to 40 nmol X kg-1) did not influence heart rate. SK, kassinin and eledoisin were more potent than SP and physalaemin in increasing respiratory insufflation pressure. The effect of SK had a particularly long duration. Neuromedin K only induced a weak increase in insufflation pressure at a very high dose. All tachykinins except neuromedin K induced an increase in vascular permeability to plasma proteins in many visceral organs, as indicated by Evans blue extravasation. The trachea and ureter were the most sensitive organs with regard to this effect. Physalaemin and eledoisin were generally more potent in increasing vascular permeability in various organs than SP and SK. The maximal permeability-increasing effect of SK was smaller than that of SP, although the potency was similar. Bombesin increased insufflation pressure with no clearcut effects on vascular permeability. It is concluded that in the same species, i.e. guinea-pig, several tachykinins have rather similar hypotensive action, while the vascular permeability increase to plasma proteins is especially pronounced after physalaemin and eledoisin. SK, kassinin and eledoisin have prominent bronchoconstrictor effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of cardiovascular and bronchoconstrictor effects of substance P, substance K and other tachykinins. 608 17

Immunofluorescence and immunoperoxidase techniques were used to study the distribution of substance P-like immunoreactivity in the intramural nerve plexuses of the guinea-pig ureter. In light microscopical preparations, immunoreactivity was observed in plexuses related to the muscle coat as well as in plexuses in the submucosa and beneath the epithelium. Ultrastructural examination showed that the immunoreactivity was located primarily in axons in the nerves. In perfusion-fixed specimens, there was evidence of its presence both in axons with terminals containing mainly large dense-cored vesicles and in axons with terminals containing mainly small vesicles. The presence of substance P-like immunoreactivity in axons with terminals containing mainly large dense-cored vesicles was supported by examination of specimens treated in vitro with capsaicin. In these specimens, the axons were dilated and showed a number of other changes in fine structure. There was also a substantial reduction in the amount of immunoreactivity in the nerve plexuses and the dilated axons contained little if any reaction product. The possibility that axons which contained large amounts of reaction product after treatment with capsaicin represented axons with terminals containing mainly small vesicles was discussed. Comparison of the distribution of the different types of small vesicle-containing terminal identified in glutaraldehyde-fixed material with that of axons containing reaction product suggested that the immunoreactivity present in such axons was located in those in which the small vesicles in the terminals were clear rather than those in which the vesicles contained dense material.
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PMID:Substance P-like immunoreactivity in the intramural nerve plexuses of the guinea-pig ureter: a light and electron microscopical study. 617 67


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