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)

[3H]Senktide, a highly selective tachykinin NK3 receptor agonist, was used to study tachykinin NK3 receptors of rat and guinea pig brain. Guinea pig brain membranes had a Kd of 3.9 +/- 0.5 nM and a Bmax of 42 fmol/mg. Dose-displacement experiments with neurokinins and selective tachykinin receptor agonists revealed the following order of potency: [MePhe7]neurokinin B > neurokinin B > substance P > neurokinin A. This order is typical for a tachykinin NK3 receptor. To further characterize the specificity of this receptor, the effects of unrelated compounds such as: bradykinin, angiotensin II, bombesin and their structural analogs were also evaluated on the binding of [3H]senktide. Unexpectedly, the angiotensin AT1 receptor antagonists, DuP 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[2'-(1H-tetrazol-5-yl)bip hen yl-4-yl)methyl]imidazole potassium salt), L-158,809 (5,7-dimethyl-2-ethyl-3-[(2'-(1H-tetrazol-5-yl) [1,1'-biphenyl]-4-yl) methyl]-3H-imidazo[4,5-beta]pyridine H2O) and EXP 3174 (2-n-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]i midazole- 5-carboxylic acid), inhibited the binding of [3H]senktide to its receptor in the guinea pig brain membranes with IC50 values of 18 microM, 25 microM and 50 microM, respectively. Similar effects were also observed with rat brain membranes. Angiotensin II, saralasin ([Sar1,Val5,Ala8]angiotensin II, a peptide angiotensin AT1 receptor antagonist) and PD 123,319 (1-[4-(dimethylamino)3-methylphenyl]methyl-5-(diphenylacetyl)-4,5, 6,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid, a known non-peptide angiotensin AT2 receptor antagonist) did not inhibit the binding of [3H]senktide to either type of membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Non-peptide angiotensin receptor antagonists bind to tachykinin NK3 receptors of rat and guinea pig brain. 751 91

1. The cardiovascular and behavioural effects elicted by the intracerebroventricular (i.c.v.) injection of substance P (SP), neurokinin A (NKA), [MePhe7]neurokinin B ([MePhe7]NKB) or angiotensin II (AII) in the conscious rat were assessed before and 5 min after i.c.v. pretreatment with antagonists selective for angiotensin AT1 (losartan and its active metabolite EXP 3174), angiotensin AT2 (PD 123,319) or tachykinin NK3 (R 486) receptors. 2. I.c.v. administration of 25 pmol AII evoked an increase in mean arterial blood pressure (MAP) and water intake behaviour, accompanied by a transient bradycardia, whereas 25 pmol [MePhe7]NKB caused a transient increase in MAP and heart rate (HR) concurrently with marked wet dog shake behaviour. At the same dose, SP and NKA were more potent than [MePhe7]NKB in increasing MAP and HR, but did not produce water intake or wet dog shake behaviours. 3. Losartan (650 pmol, i.c.v.) reduced significantly the cardiovascular and behavioural responses to AII or [MePhe7]NKB, but not to SP or NKA. While 65 pmol losartan was inactive, 260 pmol inhibited selectively the central effects of AII. Whereas EXP 3174 (6.5 nmol) blocked both AII and [MePhe7]NKB-mediated responses, the dose of 650 pmol blocked only the responses to AII. 4. The central responses to AII and [MePhe7]NKB were not affected by PD 123,319 (650 pmol). On the other hand, the [MePhe7]NKB-induced central effects were significantly reduced by R 486 (650 pmol). The NK3-selective antagonist had no effect against AII. 5. This study provides functional evidence, to support earlier binding data, that losartan (and to some extent its active metabolite EXP 3174) interact with the tachykinin NK3 receptor in rat brain. However,the cardiovascular and behavioural responses induced by central tachykinin agonists (SP, NKA and[MePhe7]NKB) and All are mediated by unrelated mechanisms.
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PMID:Functional interaction between losartan and central tachykinin NK3 receptors in the conscious rat. 754 Dec 80

Urotensin II is a cyclic undecapeptide which activates the GPR14 receptor and exerts potent vasoconstrictor effects in some species of fish and mammals. The present study intended to investigate isolated vessels from various species in an attempt to find sensitive preparations to be used in studies of the human urotensin (hU-II)/GPR14 system. Contractile responses evoked by noradrenaline (NA), angiotensin II (Ang II), endothelin 1 (ET-1) and hU-II were measured in large vessels (aorta and some large arteries and veins) of rats, guinea pigs, rabbits, pigs and humans. Relaxing effects of hU-II, bradykinin (BK) and substance P (SP) were measured in pig coronary arteries contracted with KCl 30 mM. The rat mesenteric vasculature was investigated from the arterial and venous site to establish the function of ET-1 and hU-II receptors. Results indicate that the only preparation showing high sensitivity to hU-II (pEC(50)=8.27) is the rat aorta, whose contractions in response to hU-II develop slowly and persist for hours, similar to those of ET-1 (pEC(50)=8.35). Effects of NA (pEC(50)=8.12) and Ang II (pEC(50)=7.95) develop and reverse more rapidly. Tissues treated with ET-1 and hU-II show marked desensitization, in contrast to those treated with NA. Specific antagonists for alpha(1) (prazosin, p A(2)=10.46), AT(1) (EXP 3174, p A(2)=10.20), 5HT(2) (ketanserine, p A(2)=8.61) and ET(A)-ET(B) (bosentan, p A(2)=6.88) receptors were shown to block the effects of the respective agonists, while being inactive against hU-II. In some vessels, hU-II behaved as an highly potent but scarcely effective contractile agent. It is concluded that: the hU-II/GPR14 is not a functional contractile system in vessels of several species, in contrast with NA/alpha(1), Ang II/AT(1), 5HT/5HT(2) and ET-1/ET(A)-ET(B). The rat aorta appears however to be a sensitive and reliable preparation for evaluating biological activities of hU-II and related peptides.
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PMID:Effects of human urotensin II in isolated vessels of various species; comparison with other vasoactive agents. 1181 32