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)

1. A simple desensitization protocol was set up using capsaicin and isolated, spontaneously beating atria of guinea-pigs to assess the possible participation of cardiac, capsaicin-sensitive, substance P (SP)- and calcitonin gene-related peptide (CGRP)-containing sensory nerve fibres, in the cardiac stimulatory effects of bradykinin (Bk), kallidin (Kd), 5-hydroxytryptamine (5-HT), histamine, prostaglandin E2 (PGE2), prostaglandin E1 (PGE1), prostaglandin F2 alpha, (PGF2 alpha), adrenaline (Ad), glucagon, nicotine and angiotensin II (AII). 2. The positive chronotropic and inotropic effects of Bk, Kd and 5-HT were markedly reduced in capsaicin-desensitized atria compared to control. The percentage inhibition of the chronotropic and inotropic responses to the three agonists seemed to be inversely related to the concentration of agonist used and to vary also with the type of cardiac effect produced by the drug (for Bk the percentage inhibition was: 36-81% (chronotropic effect) and 62-86% (inotropic effect); for Kd: 61-78% (chronotropic effect) and 53-77% (inotropic effect); for 5-HT: 25-66% (chronotropic effect) and 40-64% (inotropic effect]. 3. The positive chronotropic and inotropic effects of histamine, PGE1, PGE2, PGF2 alpha, glucagon and AII had similar amplitudes in capsaicin-desensitized and control atria. 4. The positive chronotropic and inotropic effects of Ad and nicotine were differentially affected by capsaicin desensitization. The inotropic effects of 7.5 x 10(-7) and 7.5 x 10(-6) M Ad were reduced by 41 and 27% respectively, in capsaicin-desensitized atria compared to control. The chronotropic effects of 1.54 x 10(-5) and 6.17 x 10(-5) M nicotine were inhibited by 57 and 26% respectively, by capsaicin desensitization. On the other hand, the chronotropic effect of Ad and the inotropic action of nicotine were of similar amplitude in capsaicin-desensitized and control atria. 5. These results were taken as an indication that a substantial part of the chronotropic and inotropic effects of Bk, Kd or 5-HT in guinea-pig atria, unlike those of histamine, PGE1, PGE2 PGF2 alpha, glucagon and AII, might be the result of stimulation of capsaicin-sensitive, SP- and CGRP- containing sensory nerve fibres. The slight, differential inhibition of the chronotropic and inotropic effects of Ad and nicotine by capsaicin desensitization suggests a minor contribution by cardiac, capsaicin-sensitive sensory nerve fibres to the effects of nicotine and Ad in guinea-pig atria.
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PMID:Effects of capsaicin desensitization on the stimulatory effect of kinins, prostaglandins, biogenic amines and various drugs in guinea-pig isolated atria. 272 Feb 92

In infant rats, kassinin exerts its antidipsogenic effect in the very early stages of neonatal life (2nd-3rd day). The inhibition of cell-dehydration drinking appears in rats of 2 days, and attains adult levels in pups of 9 days. Instead, the thirsts induced by suckling deprivation or by intracerebroventricular angiotensin II are inhibited by kassinin precociously (3rd day), but are unaffected by it in rats of 12-15 days. Kassinin also inhibits milk intake very early (3rd day) and this effect also disappears at 12 days of age. The pattern of ontogenetic results described here may be that of a brain kassinin-like tachykinin that, in the course of the development of the neural structures on which it acts, gains potent and selective control of cell-dehydration thirst.
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PMID:The development in infant rats of kassinin's potent and selective control of cell-dehydration thirst. 274 16

Neurons with intrinsic pacemaker activity and presumed sympathoexcitatory function were recorded in rat tissue slices within the confines of the rostroventrolateral reticular nucleus (RVL). These cells were excited in dose-dependent fashion by arginine vasopressin (AVP, 10(8)-10(6) M) but not by oxytocin (up to 10(7) M). The effect of AVP was mimicked by the V1-selective agonist [Phe2,Orn8]vasotocin (VT) (1 microM) but not by the V2-agonist [Val4,D-Arg8]vasopressin (VP) (1.9 microM). The effect of AVP (10(-7) M) was completely blocked by SKF 101926 (10(7) M), a non-selective antagonist and by d(CH2)5[Tyr(Me)2]AVP, a V1-selective antagonist but was unaffected by the V2-selective antagonist d(CH2)5[D-Ile2,Ile4,Ala-NH2 9]AVP. These cells were also activated by thyrotropin-releasing hormone (TRH) (10(-7)-10(-6) M), calcitonin gene-related peptide (CGRP) (4 X 10(-8) M), substance P, (10(-6) M), neuropeptide Y (NPY) (10(-8) M) and inhibited by Met-enkephalin (10(-6) M) and morphine (2 mM). Corticotropin-releasing factor (CRF) (10(-7) M) and angiotensin II (10(-6) M) were ineffective. In conclusion, RVL pacemaker neurons have vasopressin receptors reminiscent of the V1 (vascular and pressor) subtype. Their pacemaking activity is modulated by low doses of several other peptides also known to produce large vasomotor effects after introduction into the cerebroventricular space.
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PMID:Effects of vasopressin and other neuropeptides on rostral medullary sympathoexcitatory neurons 'in vitro'. 275

The objective of this study was to elucidate the mechanisms by which bradykinin and vasoactive intestinal polypeptide (VIP) relax bovine intrapulmonary artery and bradykinin, but not VIP, relaxes intrapulmonary vein. Bradykinin and VIP elicited entirely endothelium-dependent relaxation of phenylephrine-precontracted arterial rings, and this was associated with arterial accumulation of both guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP). Bradykinin, but not VIP, relaxed precontracted venous rings and increased cGMP, but not cAMP levels, by endothelium-dependent mechanisms. Neither arteries nor veins relaxed in response to substance P, thrombin, bombesin, arginine vasopressin, or angiotensin II. Methylene blue or indomethacin each partially antagonized, whereas both, when together, abolished arterial relaxant responses to bradykinin and VIP. Methylene blue or indomethacin, respectively, abolished arterial cGMP or cAMP accumulation elicited by bradykinin and VIP. Venous relaxation and cGMP accumulation elicited by bradykinin was abolished by methylene blue but was unaltered by indomethacin. Thus bradykinin and VIP relaxed bovine intrapulmonary artery by endothelium-dependent mechanisms involving the actions of cGMP and cAMP whose formation may be stimulated by endothelium-derived relaxing factor and prostacyclin, respectively. In contrast, bradykinin relaxed intrapulmonary vein by endothelium-dependent mechanisms involving only cGMP.
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PMID:Mechanisms of endothelium-dependent vascular smooth muscle relaxation elicited by bradykinin and VIP. 282 43

The results of the present study show that the intracerebroventricular injection of neurokinin A elicited a selective antidipsogenic effect in the rat. Neurokinin A proved to be an extremely potent inhibitor of drinking elicited by subcutaneous administration of hypertonic NaCl, and produced also a statistically-significant inhibition of food-associated drinking. On the other hand, it did not affect drinking evoked by other dipsogenic determinants, such as water deprivation and intracerebroventricular injection of carbachol or of angiotensin II. Thus, neurokinin A shows a spectrum of antidipsogenic activity clearly different from that of substance P, the other mammalian tachykinin so far tested on drinking behaviour in the rat, which appears to be a non-selective antidipsogenic agent. The findings of the present study suggest that different tachykinins, endogenous to the brain of the rat, might subserve distinct roles in the control of drinking behaviour.
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PMID:Neurokinin A selectively inhibits water intake in the rat. 284 71

The effect of bradykinin on the neuroeffector junction of the isolated rat vas deferens was studied in tissues stimulated transmurally at a frequency of 0.15 Hz. Bradykinin caused two distinct and independent actions: it potentiated the magnitude of the muscular response to the electrically driven twitches and, in addition, contracted the smooth muscle generating an increased muscular tone. The former action is referred to as the neurogenic or presynaptic effect, whereas the latter effect is called the musculotropic or postjunctional action. The neurogenic effect was abolished by tetrodotoxin or tissue denervation either by cold storage or chemical sympathectomy after 6-hydroxydopamine administration. However, these procedures did not significantly modify the musculotropic potency of bradykinin. Both actions of the peptide are receptor-mediated, as minor structural modifications in the amino acid sequence caused significant changes in biological potency. In addition, the peptide analog, [Thi5,8-D-Phe7]-bradykinin, behaved as an agonist at the presynaptic site but as an antagonist at the muscular site. The most potent peptide analog to produce the neurogenic effect was Met-Lys-bradykinin followed by Lys-bradykinin and [Tyr8]-bradykinin. In contrast, the potency of these peptide analogs acting at the postsynaptic site was about the same. des Arg9 bradykinin and des Arg9-[Leu8]-bradykinin were inactive at the pre- and postjunctional site. The neurogenic action of bradykinin was not mimicked by angiotensin II, neurotensin, substance P or vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of pre- and postsynaptic bradykinin receptor sites in the vas deferens: evidence for different structural prerequisites. 288 2

Agonist-induced accumulation of [3H]inositol-1-phosphate ([3H]IP1) was studied using human embryonic pituitary tumour cells (Flow 9000). Stimulation of Flow 9000 cells, prelabelled with [3H]inositol, with the nonapeptide bradykinin (BK), or its analogues and fragments produced a differential accumulation of [3H]IP1. BK-related peptides exhibited the following rank order of potency in this assay: BK = [Lys]BK greater than [Met-Lys]Bk much greater than [Des-Arg9]BK much greater than BK(1-6) = BK(2-7) = BK(2-9). BK and [Lys]BK produced half-maximal effects at 2-3 nM. [3H]BK receptor binding studies showed that BK and [Des-Arg9]BK produced a concentration-dependent inhibition of [3H]BK binding with Ki values of 4.8 +/- 1.9 nM (n = 3) and 6.8 +/- 0.7 microM (n = 3) respectively. These studies suggest the presence of B2-bradykinin receptors on the human embryonic pituitary tumour cell-line which appear to be coupled to the phosphatidyl inositol turnover signal transduction mechanism. Cholecystokinin, angiotensin II, vasopressin, thyrotropin-releasing hormone and bombesin also stimulated [3H]IP1 production but were generally much weaker than BK. In contrast, substance P, eledoisin, somatostatin, neurotensin, VIP, NPY, CGRP, U50488, DAGO and DADLE appeared inactive in this system at 10 microM.
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PMID:Bradykinin-induced accumulation of [3H]inositol-1-phosphate in human embryonic pituitary tumour cells by activation of a B2-receptor. 289 11

We have reported that microinjection of angiotensin II (ANG II) into the nucleus tractus solitarius of urethan-anesthetized normotensive rats produces an increase in mean arterial pressure (MAP) over the dose range 50-500 pmol. The effect in spontaneously hypertensive rats (SHR) is now reported. Over the range 100-500 pmol SHR exhibit increases in MAP and heart rate greater than Wistar-Kyoto or Sprague-Dawley rats. SHR did not exhibit exaggerated responses to intravenous phenylephrine, suggesting a central site of increased responsiveness to ANG II. We also found depressor effects in Sprague-Dawley at lower doses (0.1 and 1 pmol). The decreases in MAP were extremely variable and not dose related. A selected dose of additional neuropeptides identified in the NTS was tested. Somatostatin, bradykinin, and vasoactive intestinal peptide (0.5 nmol) were without cardiovascular effects. Oxytocin and vasopressin, however, produced significant increases in MAP. Substance P produced a very small but significant increase in heart rate and MAP. Interaction between the vasopressin and ANG II pressor effects was studied, and each proved to be independent.
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PMID:Neuropeptide action in nucleus tractus solitarius: angiotensin specificity and hypertensive rats. 293 Oct 31

Picomolar concentrations of neurotensin caused concentration-dependent contractions of the longitudinal musculature of the fundus of the rat stomach. The EC50 of neurotensin was approximately 1.5 nM. On a molar basis neurotensin was about 5-10 times more potent than 5-hydroxytryptamine (5-HT) and approximately 80 times as active as acetylcholine in producing similar contractions. Studies with structurally related peptides indicated that whereas the carboxy terminal portion of neurotensin was essential for biological activity, a substantial part of its amino terminus end could be removed without affecting its potency. The EC50 for the neurotensin fragment 8-13 was identical to that of neurotensin, however its 1-8 or 1-11 fragments were completely inactive. Tetrodotoxin did not modify the potency of neurotensin or structurally related analogues suggesting that the neurotensin receptor is probably located on the smooth muscle membrane. In addition, the potency of neurotensin in contracting the fundus was not modified by pretreatment with atropine, methysergide or diphenhydramine. Fade to the contractile response of neurotensin was followed by the development of tachyphylaxis; desensitization was concentration-dependent and characterized by a shift in the agonist concentration-response curve to the right and downwards. Desensitization with a priming concentration of neurotensin (approx. EC50) caused a substantial blockade of its excitability. There was cross-desensitization between neurotensin and the contractile activity of neurotensin 8-13 or xenopsin, but not with angiotensin II, bradykinin, substance P, acetylcholine, 5-HT or histamine. Pretreatment of the fundus strip with verapamil 0.3-1 microM antagonized in a concentration-dependent fashion the neurotensin-induced contractions but not the muscular contractions caused by acetylcholine. It is concluded that neurotensin activates a specific excitatory receptor probably located on the cell membrane of the smooth muscles of the rat fundus. In addition, we suggest that this receptor is somehow related to a voltage-dependent calcium channel, sensitive to verapamil.
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PMID:Excitatory neurotensin receptors on the smooth muscle of the rat fundus: possible implications in gastric motility. 298 83

A dipeptidyl carboxypeptidase, which cleaved the Gly3-Phe4 bond of enkephalins, was purified from guinea pig serum 420-fold. The optimum pH of the enzyme was in the neutral range (pH 7.25), and the molecular weight was estimated to be approx. 280,000. The enzyme hydrolyzed Met- and Leu-enkephalin with Km values of 0.30 and 0.50 mM, respectively. The enzyme was inhibited by metal chelators and p-chloro-mercuribenzoate. Captopril showed high inhibitory potency, while phosphoramidon and Phe-Ala showed no effect on the enzyme activity. Therefore, the obtained enzyme can be classified as an angiotensin-converting enzyme (EC 3.4.15.1). Among the bioactive peptides examined, bradykinin and angiotensin I were hydrolyzed by the enzyme. Angiotensin III showed a stronger inhibitory effect than that of angiotensin II. Substance P, gastrin I, and secretin were also inhibitory toward the enzyme activity. On high-performance liquid chromatography analysis, Met-enkephalin-Arg6-Phe7 and Leu-enkephalin-Arg6 were cleaved sequentially at the second peptide bond of the C terminus. Thus, the dipeptidyl carboxypeptidase in guinea pig serum may play a role not only in the angiotensin-bradykinin system but also in the metabolism of circulating enkephalins and other bioactive peptides.
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PMID:Enkephalin-degrading dipeptidyl carboxypeptidase in guinea pig serum: its properties and action on bioactive peptides. 299 Mar 46


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