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)

A method for determining the vocalization response to algesic agents in conscious guinea pigs is described. Retrograde injection of small amounts of algesic agents into the femoral artery caused transient but obvious vocalization response in a dose-dependent manner. The vocal sound was converted into electrical signals and the envelope of the sound obtained by a peak detector circuit was recorded on an ink-writing oscillograph. The area of the vocalization response circumscribed by a base line and the envelope tracing of the vocal sound was also recorded. Bradykinin, kallidin, acetylcholine (ACh) and nicotine caused the vocalization response, while substance P, histamine, bethanechol, methacholine, serotonin, kallikrein and prostaglandins E1 and E2 caused no or little response. No detectable tachyphylaxis to bradykinin, ACh and nicotine was observed. The pretreatment with hexamethonium abolished the response induced by ACh or nicotine but not the response induced by bradykinin. These results suggest that the paravascular pain receptor of the femoral artery excited by ACh is nicotinic in character. Subcutaneous injection of morphine, pentazocine, diclofenac and aminopyrine inhibited the vocalization response induced by bradykinin in a dose-dependent manner.
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PMID:Vocalization response to close-arterial injection of bradykinin and other algesic agents in guinea pigs and its application to quantitative assessment of analgesic agents. 43 Mar 71

Investigations on various kinds of biological actions of a newly purified hypothalamic tridecapeptide, neurotensin, were performed both in vivo and in vitro by utilizing experimental animal models. The effect of neurotensin on pituitary gonadotropin release was studied in ovariectomized estrogen-progesterone-treated rats by the measurement of serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) in radioimmunoassays. Neurotensin (340 mg/100 g BW) significantly increased serum LH and FSH 30 minutes after an intravenous injection (p smaller than 0.05) and lowered serum prolactin concentrations significantly (p less than 0.025). Bradykinin and substance P showed on significant effect on serum LH and FSH release. Intraperitoneal or intravenous administration of 0.5 n.mole neurotensin lowered blood pressure in intact mature rats from the range of 90 approximately 100 mmHg to 50 approximately 60 mmHg; however, tachyphylaxis was observed after repeated injections of the same dose of this peptide. Neurotensin was as potent as bradykinin in inducing rat duodenum relaxation and guinea pig ileum contraction in vitro. Theses effects on neurotensin and bradykinin on the intestines were not inhibited by the pre-treatment of phentolamine, propranolol, methysergide and pyribenzamine. Bradykinin induced contractions of the uterus in proestrous rats, but neurotensin induced no marked contraction. These results suggest that neurotensin in not hypothalamic releasing or inhibiting factor but possess the nature of kinin.
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PMID:[A study on the biological action of hypothalamic tridecapeptide, neurotensin (author's transl)]. 43 7

1. The release of PGs from the isolated perfused rabbit ear was measured by means of a radioimmunoassay. 2. Bradykinin in dose dependent amounts released mainly PGE (presumably PGE1) and in much smaller amounts also PGF. 3. Bradykinin released similar amounts of PGE in innervated and chronically denervated ears. 4. Indomethacin completely prevented the PGE release by bradykinin. 5. ACh showed a much lower efficacy than bradykinin in releasing PGE and PGF. Synthetic substance P was devoid of any PGE releasing action. 6. It is concluded that bradykinin increases its own algesic action by a concomitant rapid stimulation of the PGE synthesis, thus providing a mechanism for the facilitation of its own algesic action.
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PMID:Release of prostaglandins by bradykinin as an intrinsic mechanism of its algesic effect. 100 30

In primary cultures of dog tracheal epithelium, isoproterenol produced a transient increase in short-circuit current (Isc) (duration 30 s; maximal increase, 32 +/- 5 microA/cm2). This was followed by a more slowly developing sustained increase (9 +/- 3 microA/cm2), which mimicked the response to N6, 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP). The transient and sustained responses had dissociation constants for isoproterenol of 2 x 10(-8) and 2 x 10(-9) M, respectively. Bradykinin (in the presence of indomethacin), substance P, histamine, and thrombin produced only transient increases in Isc. The time courses of these transients closely paralleled changes in concentration of intracellular Ca ([Ca2+]i) as measured with fura 2. For different mediators, there was a significant correlation between the maximal transient increase in Isc and the maximal increase in [Ca2+]i. The transients in Isc were not associated with elevation of adenosine 3',5'-cyclic monophosphate (cAMP) and were unaffected by pretreatment with DBcAMP, which abolishes the steady-state increase in response to isoproterenol. Both the transient increases in Isc and [Ca2+]i were inhibited by pretreatment with the Ca chelator 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate abolished the transient increases in [Ca2+]i and Isc in response to isoproterenol but not to bradykinin. These results provide evidence that 1) isoproterenol and bradykinin elevate [Ca2+]i by different mechanisms, and 2) Ca elevation is associated with a transient increase in Isc, whereas increased cAMP is associated with a smaller sustained increase.
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PMID:Calcium-dependent regulation of Cl secretion in tracheal epithelium. 131 17

The local motor response to bradykinin and the bacterial chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated in the guinea-pig isolated renal pelvis and ureter in relation to possible activation of capsaicin-sensitive primary afferent nerves and release of sensory neuropeptides. Both bradykinin (1 nM-10 microM) and FMLP (10 nM-10 microM) produced a concentration-dependent positive inotropic effect in the isolated renal pelvis which was unaffected by in vitro capsaicin desensitization. The response to bradykinin was antagonized by HOE 140, a bradykinin receptor antagonist, while it was unaffected by MEN 10,376, a tachykinin receptor antagonist, hCGRP(8-37) a calcitonin gene-related peptide (CGRP) receptor antagonist and N-t-BOC-Phe-DLeu-Phe-DLeu-Phe (BPLPLP), an FMLP antagonist. The response to FMLP was blocked by BPLPLP while it was unaffected by HOE 140, MEN 10,376 or hCGRP(8-37). Indomethacin (10 microM) enhanced the response to both bradykinin and FMLP. Bradykinin transiently activated rhythmic contractions in the isolated ureter. The response to bradykinin was blocked by HOE 140 and was unaffected by in vitro capsaicin desensitization, indomethacin, MEN 10,376 or BPLPLP. FMLP had no motor effect on the resting ureter but when rhythmic background contractions were evoked by the addition of 100 nM endothelin 1, it produced a transient suppression of ureteral motility. This inhibitory effect was unchanged by in vitro capsaicin desensitization or HOE 140 while it was abolished by indomethacin or BPLPLP pretreatment. Both bradykinin and FMLP evoked the release of CGRP-like immunoreactivity in the renal pelvis. The effect of bradykinin but not that of FMLP was abolished by indomethacin. By contrast neither bradykinin nor FMLP did evoke a significant CGRP-LI release in the ureter. It is concluded that bradykinin and FMLP affect pyeloureteral motility through specific and independent pathways. The local motor responses produced by these chemical stimulants are independent from the release of sensory neuropeptides from capsaicin-sensitive primary afferent neurons. Direct neurochemical evidence was obtained for activation of capsaicin-sensitive primary afferents in the renal pelvis: such a mechanism could be involved in the genesis of ureteral pain whenever bradykinin or FMLP come into contact with sensory nerves in the pyeloureteral wall.
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PMID:Local motor responses to bradykinin and bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) in the guinea-pig isolated renal pelvis and ureter. 133 50

Bradykinin (BK) has been reported to have mixed excitatory/inhibitory effects on gastrointestinal motility. The present study examined the mechanism responsible for the inhibition of gastric motor activity caused by intraperitoneal administration of BK. Gastric motor activity was measured by recording the intragastric pressure (IGP) of phenobarbital-anesthetized rats via a transesophageal catheter. To facilitate the study of inhibitory influences, gastric motility was stimulated by neurokinin A (NKA), which on intravenous injection evoked reproducible gastric contractions as measured by a rise of IGP. Intraperitoneal injection of BK (0.1-10 nmol) inhibited the NKA-induced increase in IGP in a dose-dependent manner, and the effect of epigastric administration of BK was not significantly different from that of intraperitoneal administration. The inhibitory effect of intraperitoneal BK on gastric motility was due to an effect on BK2 receptors because it was blocked by prior intraperitoneal injection of the BK2 antagonist Hoe 140. The specificity of this BK antagonist was demonstrated by its inability to antagonize the effect of intraperitoneal hydrochloric acid (HCl), which, like BK, inhibited the NKA-induced gastric contractions. Because the BK- and HCl-induced inhibition of the NKA-induced rise of IGP was abolished by acute removal of the celiac-superior mesenteric ganglion complex, but left unaltered by acute bilateral subdiaphragmatic vagotomy, it is inferred that intraperitoneal BK inhibits gastric motor activity via activation of an autonomic reflex that involves prevertebral ganglia.
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PMID:Reflex gastric motor inhibition caused by intraperitoneal bradykinin: antagonism by Hoe 140, a bradykinin antagonist. 133 75

Axon reflex mechanisms may be involved in the pathogenesis of asthma, but there has been no direct evidence that endogenous tachykinins cause bronchoconstriction in asthmatic subjects. We have studied the effect of a tachykinin receptor antagonist (FK-224) on bronchoconstriction induced by inhalation of bradykinin in asthmatic patients. In a double-blind, placebo-controlled, crossover trial, ten subjects with stable asthma were given FK-224 (4 mg) or placebo by inhalation 20 min before challenge with bradykinin (0-1250 micrograms/ml, five breaths of each concentration) given with 5 min intervals. Bradykinin caused dose-dependent bronchoconstriction in all subjects. FK-224 significantly opposed the bronchoconstrictor effect; the geometric mean of the cumulative concentration required to elicit a 35% fall in specific airway conductance was 5.3 micrograms/ml after placebo and 40 micrograms/ml after FK-224 (p < 0.001). Inhalation of bradykinin caused coughing in three subjects, which was inhibited by FK-224 in all three. Antagonism of the tachykinin receptor by FK-224 greatly inhibited both bronchoconstriction and coughing induced by bradykinin in asthmatic patients, suggesting that tachykinin release from the airway sensory nerves is involved in responses to bradykinin. Tachykinin receptor antagonists may be useful in the treatment of asthma.
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PMID:Protection against bradykinin-induced bronchoconstriction in asthmatic patients by neurokinin receptor antagonist. 135 19

1. Release of endothelium derived relaxing factor (EDRF) and prostacyclin (PGI2) from endothelial cells (EC) cultured from bovine aortae was measured by bioassay and radioimmunoassay, respectively, during infusions (10 min) of bradykinin (BK), adenosine diphosphate (ADP), arachidonic acid (AA), alkaline buffers and the free-bases (FB) of L-arginine or D-arginine. Release of EDRF from the luminally perfused rabbit aorta was also measured during infusions (10 min) of acetylcholine (ACh), substance P and ADP. 2. Bradykinin (10 or 30 nM) infused through the column of EC induced release of both EDRF and PGI2, neither of which was maintained for the duration of the infusion. 3. ADP (1.6 or 4 microM) infused through the column of EC induced release of a EDRF which was maintained for the duration of the infusion and a release of PGI2 which lasted for a much shorter period. 4. Arachidonic acid (30 or 90 microM) infused through the column of EC caused a sustained release of EDRF and PGI2, both of which outlasted the infusion of AA. 5. L-Arginine FB, D-arginine FB or alkaline buffer infused through the column of EC released EDRF, but only small amounts of PGI2. The release of EDRF outlasted the period of infusion and was due to an increase in the pH of the Krebs solution perfusing the EC. 6. Infusions of ACh (0.25-1 microM) or ADP (4-16 microM) caused a sustained release of EDRF from the luminally-perfused rabbit aorta, whereas infusion of substance P (3.3-10 microM) caused only a transient release of EDRF. 7. These results show that distinct patterns of EDRF release exist to different agonists in both cultured and in situ EC, and that EDRF and PGI2 do not necessarily follow the same time course of release. Furthermore, sustained release of EDRF does not require the constant infusion of the precursor, L-arginine, whereas sustained release of PGI2 only occurs when AA, the precursor of PGI2, is present in the extracellular medium.
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PMID:Different patterns of release of endothelium-derived relaxing factor and prostacyclin. 137 3

The effect of resiniferatoxin on the isolated iris sphincter muscle of the rabbit was compared with the effects of capsaicin and bradykinin. The three compounds all contracted the sphincter muscle in a concentration-dependent manner. The contractions were inhibited by spantide II, a tachykinin antagonist. The concentration-response curve of resiniferatoxin was biphasic, yielding two EC50 values, one about 10,000 times lower than the other, the latter value being similar to that for capsaicin. The responses to resiniferatoxin, capsaicin or bradykinin were progressively reduced upon repeated application. The contraction evoked by either of the three compounds was not affected by thiorphan (an enkephalinase inhibitor) or captopril (an angiotensin-converting enzyme inhibitor). Pretreatment with capsaicin concentration dependently reduced the contractile response to a subsequent application of resiniferatoxin and vice versa. Bradykinin pretreatment reduced the resiniferatoxin response by about 50%; resiniferatoxin pretreatment completely abolished the response to bradykinin. Also, the contractile response to electrical stimulation was reduced concentration dependently by resiniferatoxin, capsaicin and bradykinin pretreatment. The response to electrical stimulation could be completely abolished by pretreatment with large doses of resiniferatoxin or capsaicin; pretreatment with large doses of bradykinin reduced the response by about 50%. Pretreatment with high concentrations of resiniferatoxin, or capsaicin, but not bradykinin, reduced the contractile response to the NK1 receptor agonist, [Sar9, Met(O2)11]SP (10(-8) M). The results suggest that the three compounds produce tachyphylaxis, mainly through partial (bradykinin) or complete (capsaicin, resiniferatoxin) exhaustion of the neuronal pool of releasable tachykinins although desensitization of tachykinin receptors may also contribute.
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PMID:Effect of resiniferatoxin on the isolated rabbit iris sphincter muscle: comparison with capsaicin and bradykinin. 138 78

Kinins and substance P have been implicated in the pathogenesis of inflammatory arthritis by virtue of their abilities to induce vasodilation, edema, and pain. The relative biological potencies of these peptides in vivo would depend at least in part upon their rates of catabolism in the joint. We hypothesized that human synovial lining cells may regulate intraarticular levels of kinins and neuropeptides via degradation by cell surface-associated peptidases. We exposed intact human synovial fibroblasts to kinins and substance P, in the presence or absence of specific peptidase inhibitors, and measured the amount of intact substrate remaining and degradation product(s) generated over time. Aminopeptidase M (AmM; EC 3.4.11.2), neutral endopeptidase-24.11 (NEP-24.11; EC 3.4.24.11), and dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) were identified on the cell surface of synovial cells. Bradykinin degradation was due entirely to NEP-24.11 (1.39 +/- 0.29 nmol/min per well). Lysylbradykinin was also degraded by NEP-24.11 (0.80 +/- 0.19 nmol/min per well); however, in the presence of phosphoramidon, AmM-mediated conversion to bradykinin (3.74 +/- 0.46 nmol/min per well) could be demonstrated. The combined actions of NEP-24.11 (0.93 +/- 0.15 nmol/min per well) and DAP IV (0.84 +/- 0.18 nmol/min per well) were responsible for the degradation of substance P. AmM (2.44 +/- 0.33 nmol/min per well) and NEP-24.11 (1.30 +/- 0.45 nmol/min per well) were responsible for the degradation of the opioid peptide, [Leu5]enkephalin. The identity of each of the three peptidases was confirmed via synthetic substrate hydrolysis, inhibition profile, and immunological identification. The profiles of peptidase enzymes identified in cells derived from rheumatoid and osteoarthritic joints were identical. These data demonstrate the human synovial fibroblast to be a rich source of three specific peptidases and suggest that it may play a prominent role in regulating peptide levels in the joint.
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PMID:Cultured human synovial fibroblasts rapidly metabolize kinins and neuropeptides. 138 26


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