UNIPROT:P20366 - FACTA Search

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

We studied the effects of a variety of noncholinergic, nonadrenergic agents on the smooth muscles of the cat urethra. Prostaglandin F2 alpha contracted both urethral muscle layers to a similar extent. Prostaglandin E2 contracted the longitudinal and relaxed the circular muscle layers. The effects of the prostaglandins seem to be directly myogenic since cholinergic and adrenergic blockers and tetrodotoxin did not affect them. Bradykinin and substance P contracted both urethral muscle layers. Other tested agonists (neurotensin, vasoactive intestinal peptide, cyclic 3,5 adenosine monophosphate, adenosine diphosphate sodium, cyclic 3,5 guanosine monophosphate sodium, bombesin) had no effect on the cat urethral smooth muscles.
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PMID:Response of urethral smooth muscles to pharmacological agents. II. Noncholinergic, nonadrenergic agonists and antagonists. 619 58

Polypeptides are endogenous agents, involved in the regulation of many physiologic functions and the pathogenesis of several diseases. Polypeptide antagonists form a group of new chemical entities which may provide valid therapeutic agents. Some polypeptides (angiotensin, kinins) are released through the action of proteolytic enzymes (renin, kallikreins) and act as hormones or autacoids; others (substance P, neurotensin) are synthetized by nervous cells to serve as neurotransmitters or neuromodulators. The main homeostatic role of the renin-angiotensin system is to uphold high systemic arterial blood pressure. Overproduction of renin and insufficient checking of renin secretion are among the most common causes of arterial hypertension. Several forms of arterial hypertension (neurovascular, idiopathic) benefit from a reduction in renin-angiotensin system activity. This is achieved either through decreasing renin secretion, by inhibiting conversion of angiotensin I into angiotensin II, or through blocking the peripheral actions (at the receptor sites) of angiotensin II. Renin secretion is very significantly reduced by beta-blocking agents (propranolol); conversion of angiotensin I into angiotensin II is inhibited by teprotide, captopril and their derivatives; peripheral actions of angiotensin II are blocked by saralasin. Bradykinin and related agents produce vasodilation, increase vascular permeability and stimulate pain fibers. Kinins thus reproduce the cardinal features of inflammation and are held to be mediators of the inflammatory reaction. The substance P neuropeptide is found in the brain and bowel; it may act as a transmitter of the sensation of pain at the spinal cord and central nervous system sites. Among other effects outside of the brain, substance P is a potent vasodilator and inhibits renin secretion. Neurotensin is a neuropeptide which produces hypothermia, muscular relaxation and analgesia. Outside of the brain, this peptide is involved in the regulation of gastric secretion, intestinal motility and insulin and glucagon secretion. The vasoactive intestinal peptide, found in certain cholinergic nerve endings, is a large peptide which inhibits gastric secretion, intestinal motility and vascular tone.
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PMID:[Polypeptides and antagonists]. 620 6

The isolated, circular preparations of the left and right bronchi of the rat were examined for mechanical responses to neurotensin (NT) and other vasoactive peptides. NT caused concentration-dependent increases in the isometric tension of the unstimulated preparations, with an apparent affinity higher than for the cholinergic agonists but with considerably lower intrinsic activity. Pronounced tachyphylaxis to NT was observed. NT potentiated the atropine-sensitive increase in tension resulting from electrical field stimulation. Neither atropine nor methysergide abolished the response to NT in the unstimulated preparations. Bradykinin and to a lesser extent angiotensin II contracted the unstimulated preparations and both systemic peptides enhanced the cholinergic output in response to field stimulation. Substance P and VIP on the other hand were without effects in the stimulated and unstimulated bronchi. The results are consistent with the presence of receptors for NT on the presynaptic cholinergic terminals as well as on the post-synaptic smooth muscles of the rat bronchi.
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PMID:Neurotensin receptors in the rat bronchi. 628 40

1. The nature of the non-cholinergic, non-adrenergic (non-ch., non-adr.) excitatory and inhibitory transmission in the longitudinal and circular muscle layers of the guinea-pig ileum was investigated, and the effects of various agents on the junction potentials were observed using the micro-electrode method.2. In longitudinal muscle cells, ATP (3 x 10(-5)-10(-4) M) and adenosine (10(-5)-10(-4) M) depolarized the membrane, decreased the input resistance, increased the spike activity and abolished the generation of cholinergic excitatory junction potentials (e.j.p.s).3. In the presence of atropine (10(-6) M) with guanethidine (10(-5) M), field stimulation evoked three different types of the response (non-ch., non-adr. e.j.p.s, i.j.p.s (inhibitory junction potentials) or both) from cells of the longitudinal muscle layers, and only one type of the response (non-ch., non-adr. i.j.p.s) from cells of the circular muscle layer. In the following experiments atropine and guanethidine were present in the bathing fluid for at least 20 min.4. In some longitudinal muscle cells (non-ch., non-adr. i.j.p. type), ATP (5 x 10(-6)-10(-3) M) and adenosine (10(-5)-3 x 10(-5) M) depolarized the membrane, while in other cells (non-ch., non-adr. e.j.p. type), ATP (10(-5)-10(-4) M) and adenosine (10(-5)-3 x 10(-5) M) hyperpolarized the membrane and further increases in the concentration of ATP (10(-3) M) resulted in a depolarization of the membrane.5. Apamin (10(-7)-3 x 10(-6) M) inhibited the generation of non-ch., non-adr. i.j.p.s in both longitudinal and circular muscle cells, while this agent had no effect on the non-ch., non-adr. e.j.p.s. As a consequence, in some cells of the longitudinal muscle layer (non-ch., non-adr. e.j.p. and i.j.p. type) the amplitude of e.j.p.s was enhanced in the presence of apamin. TEA (5 x 10(-3)-1.5 x 10(-2) M) suppressed the after-hyperpolarization of the spike and i.j.p.s recorded from both muscle layers, whereas the duration and amplitudes of cholinergic and non-ch., non-adr. e.j.p.s were enhanced.6. Vasoactive intestinal polypeptide (VIP; 10(-8)-10(-7) M) had no effect on the membrane potential and junction potentials of longitudinal and circular muscle layers.7. Substance P (SP; 10(-8)-10(-7) M) depolarized the membrane of cells of the longitudinal layer (non-ch., non-adr. e.j.p. type), while this agent had no effect on cells of longitudinal (non-ch., non-adr. i.j.p. type) and circular muscle layers. SP suppressed the generation of non-ch., non-adr. e.j.p.s but had no effect on i.j.p.s. Generation of non-ch., non-adr. e.j.p.s was not restored under conditions of repolarization of the membrane to the resting level by application of inward current.8. Bradykinin (BK; 10(-8)-10(-5) M) hyperpolarized the membrane and suppressed the generation of i.j.p.s in the cells of longitudinal (non-ch., non-adr. i.j.p. type) and circular muscle layers. However, when the membrane potential was displaced to the control level by outward current in the presence of BK, field stimulation evoked the i.j.p. In cells of non-ch., non-adr. e.j.p. type of the longitudinal muscle layer, BK depolarized the membrane, increased the spike activity, generated slow waves and blocked the generation of non-ch., non-adr. e.j.p.s. Displacement of the membrane potential to the control level by inward current did not restore the non-ch., non-adr. e.j.p.s.9. These results suggest that in the guinea-pig ileum ATP and adenosine probably do not contribute to the generation of non-ch., non-adr. e.j.p.s and i.j.p.s, as transmitter substances. The actions of other possible candidates such as SP and BK, are discussed.
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PMID:The nature of non-cholinergic, non-adrenergic transmission in longitudinal and circular muscles of the guinea-pig ileum. 629 75

The effect of the nonapeptide bradykinin on the membrane potential of permanent cell lines from neural origin was studied. A hyperpolarizing response of 10-30 s duration was produced when bradykinin was iontophoretically applied onto polyploid rat glioma cells (clone C6-4-2). Starting from the resting membrane potential the peak value of the hyperpolarizing response was reached within 0.5-1.5 s. Then the potential returned more slowly to the original value. The hyperpolarization was associated with an approximately 50% decrease in membrane resistance. Neither Na+ nor Cl- seemed to be important for the hyperpolarizing response, since bradykinin elicited similar hyperpolarizations in cells exposed to media in which Na+ or Cl- were replaced by choline or isethionate, respectively. Ca2+ fluxes are unlikely to be involved, since the addition of D600 did not affect the hyperpolarizations induced by bradykinin. However, a 10-fold increase in the concentration of K+ in the medium reduced the amplitude of the hyperpolarization by 40 mV. Thus, the hyperpolarization induced by bradykinin is associated with decrease in membrane resistance which is likely to be caused by an increased K+-conductance. The glioma cells showed a desensitization upon repeated application of bradykinin. However, the sensitivity of the cells to bradykinin was restored after 3-8 min of incubation in the absence of bradykinin. Since an antagonist of bradykinin is not known, the specificity of the action of bradykinin is difficult to assess. Nevertheless, the hyperpolarizing response to bradykinin appears to be specific insofar as other peptides, i.e. lutoliberin, thyroliberin, neurotensin, substance P and apamin, exerted no effect on the membrane potential of the glioma cells. Bradykinin-elicited hyperpolarizations with characteristics similar to those described above could also be demonstrated in neuroblastoma X glioma hybrid cells, but not in multinucleated fibroblast cells.
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PMID:Bradykinin induces hyperpolarizations in rat glioma cells and in neuroblastoma X glioma hybrid cells. 709 75

The modulatory effect of bradykinin on excitatory nonadrenergic noncholinergic (e-NANC) neural constrictor responses was examined in anesthetized guinea pig airways in vivo. e-NANC responses were obtained by bilateral vagal stimulation in the presence of atropine (1 mg/kg i.v.) and propranolol (1 mg/kg i.v.). Indomethacin (5 mg/kg i.v.) and captopril (1 mg/kg i.v.) were pretreated to avoid the indirect effects of bradykinin by producing prostaglandins and to prevent endogenous breakdown of bradykinin, respectively. Bradykinin (0.01-1 nmol/kg i.v.) potentiated e-NANC responses in a dose-dependent manner. The potentiation was significant with 0.1 and 1 nmol/kg of bradykinin, 22.7 +/- 3.2% (mean +/- S.E.; P < .01) and 34.5 +/- 4.7% (P < .01), respectively), compared with that in sham-injected control animals (-4.7 +/- 3.6%). The potentiation of e-NANC responses by bradykinin (1 nmol/kg i.v.) was abolished by the subsequent administration of a bradykinin B2 receptor antagonist, HOE140 (0.1 mumol/kg i.v.), that was without effect on e-NANC responses by itself. The contraction induced by exogenous administration of substance P (1 nmol/kg i.v.) was not affected by the same dose of i.v. bradykinin; the change in substance P-induced bronchoconstriction was 9.2 +/- 8.3% with and 3.2 +/- 3.6% without bradykinin (P > .05). These results suggest that bradykinin potentiates e-NANC responses in guinea pig airways in vivo via B2 receptors which are possibly on prejunctional sites.
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PMID:Modulation of nonadrenergic noncholinergic neural bronchoconstriction by bradykinin in anesthetized guinea pigs in vivo. 750 96

Bradykinin (Bk) induced a contraction in all small bronchi samples (diameter, 0.5 to 1 mm) from 20 patients. pD2 was 7.7 +/- 0.1 (pD2 = -log EC50) and maximal effect (Emax) was 36.2 +/- 4.7% of the maximal response to acetylcholine. The B2 agonist [Hyp3TyrMe8]Bk contracted airway smooth muscle with a pD2 of 7.8 +/- 0.2 and an Emax of 39 +/- 9%. The B1 agonist [Sar1dPhe8desArg9]Bk induced only a weak contraction at 10(-6) M. The effect of Bk was abolished by the B2 (Hoe 140) but not by the B1 [Leu8desArg9]Bk receptor antagonist. Indomethacin 10(-6) M abolished Bk-induced contraction, suggesting that cyclooxygenase products are involved in Bk action. Capsaicin 10(-5) M, which selectively depletes C fibers from airway mediators through the ruthenium red pathway, and ruthenium red 10(-5) M significantly inhibited the concentration-response curves to Bk. However, tetrodotoxin (+/-)-CP-96,345, SR 48968, and atropine did not significantly affect Bk concentration-response curves, suggesting that nerve conduction, substance P (SP), neurokinin A (NKA), and acetylcholine release are not involved in Bk action. Our data indicate that Bk contracts human distal airway smooth muscle through the Bk B2 receptor and a cyclooxygenase pathway. This effect appears to involve capsaicin and ruthenium red pathways but neither acetylcholine nor NKA and SP release.
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PMID:Contractile effects of bradykinin on the isolated human small bronchus. 750 45

We examined the mechanisms of bradykinin-induced airway microvascular leakage in guinea pig airways by measuring extravasation of Evans blue dye. Animals were pretreated with propranolol (1 mg/kg, intravenous) and atropine (1 mg/kg, intravenous) to block the beta-adrenergic and muscarinic responses, respectively. Bradykinin (250 nmol) instillation into airways significantly increased the leakage of dye in the trachea, main bronchi, and intrapulmonary airways to the same degree. The bradykinin B2-receptor antagonist HOE140 (500 nmol/kg, intravenous) did not alter basal leakage but almost completely inhibited bradykinin-mediated leakage. By contrast, the neurokinin NK1 antagonist FK888 (10 mg/kg, intravenous) partially inhibited bradykinin-induced leakage in trachea (p < 0.01) and main bronchi (p < 0.01), but had no significant effect on intrapulmonary airways. Indomethacin (5 mg/kg, intravenous) had no effect on the plasma leakage after instilled bradykinin. We concluded that the airway inflammatory response to bradykinin administered directly into the airways is mediated by bradykinin B2 receptors and partially mediated by tachykinin release from sensory nerve terminals, whereas cyclooxygenase products have no important role in the response. In the central airways, the contribution of sensory neuropeptides to the bradykinin response is greater than that caused by direct stimulation of the B2 receptor on the endothelium at the postcapillary venule of the bronchial circulation. In contrast, in the peripheral airways, the contribution of direct B2-receptor stimulation on the airway vasculature is greater than that involving sensory neuropeptides.
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PMID:Bradykinin-induced airway inflammation. Contribution of sensory neuropeptides differs according to airway site. 750 4

Airway responsiveness is increased in a variety of airway diseases. To understand the mechanism of enhanced airway responsiveness, in particular as it pertains to asthma, animal models have been developed and extensively explored. The guinea pig and Basenji-greyhound dog are the best characterized animals showing airways hyperresponsiveness and appear to bear substantial resemblances to asthmatic human subjects. Challenge with bronchoconstrictive agonist results in bronchoconstriction and transient vascular leak. Both phenomena contribute to the degree of airway narrowing. Adenosine challenge tests not only the responsiveness of the airways, but also that of the airway effector cells such as the mastocyte. Bradykinin and tachykinin cause indirect airway narrowing, probably by liberation of leukotrienes. Responsiveness can be enhanced by immune and non-immune challenges. Ozone, Sephadex, various contractile agonists (leukotriene D-4, bradykinin, platelet-activating factor), as well as certain cytokines (IL-1, IL-2, TNF-alpha) can enhance airway responsiveness. Cyclooxygenase and lipooxygenase products appear to be involved. Allergen-induced hyperresponsiveness is associated with airway inflammation and appears to involve bradykinin and PAF acutely and growth of airway smooth muscle chronically.
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PMID:[Animal models of bronchial hyperreactivity]. 751 8

Prostaglandins are known to enhance the inflammatory and nociceptive actions of other chemical mediators of inflammation such as bradykinin. One possible mechanism for this sensitizing action is that prostanoids augment the release of neuroactive substances from sensory neurons. To initially test this hypothesis, we examined whether selected prostaglandins could enhance the resting or bradykinin-evoked release of immunoreactive substance P (iSP) and/or immunoreactive calcitonin gene-related peptide (iCGRP) from sensory neurons in culture. Bradykinin alone causes a concentration-dependent increase in the release of iSP and iCGRP from isolated sensory neurons, and this action is abolished in the absence of extracellular calcium. Pretreating the neurons with PGE2 (10 nM to 1 microM) potentiates the bradykinin-evoked release of both iSP and iCGRP by approximately two-to fourfold. At these concentrations, PGE2 alone did not significantly alter peptide release. Exposing the cultures to 1 microM PGF2 alpha is ineffective in altering either resting or bradykinin-evoked peptide release. Sensory neurons in culture contain cyclooxygenase-like immunoreactivity suggesting that the enzyme that converts arachidonic acid to prostaglandins is present. In addition, pretreating cultures with 14C-arachidonic acid yields radiolabeled eicosanoids that cochromatograph with known prostaglandin standards. Preexposing cultures to indomethacin abolishes the production of prostaglandins and attenuates the bradykinin-stimulated release of iSP and iCGRP. This implies that the synthesis of prostaglandins contributes to the bradykinin-evoked release of peptides. The augmentation of bradykinin-induced release of iSP and iCGRP by PGE2 may be one mechanism to account for the inflammatory and hyperalgesic actions of this eicosanoid.
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PMID:Prostaglandin E2 enhances bradykinin-stimulated release of neuropeptides from rat sensory neurons in culture. 751 58

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