Functional characterization of alpha1-adrenoceptor subtypes in the rabbit spleen.
Phenylephrine and (+/-)N-[5-(4,5-dihydro-1-H-imidazol-2yl)-2-hydroxy-5,6,7,8-tetr ahydronaphthalen-1-yl] methanesulphonamide hydrobromide (A 61603) evoked concentration-dependent contractions of the rabbit spleen. These contractions were antagonized by prazosin (10(-8)-10(-7) M) with pA2 values of 8.34+/-0.11 and 8.15+/-0.10 against phenylephrine and A 61603, respectively. In both cases, the slopes of the Schild plots were not significantly (P>0.05) different from 1.0, indicating competitive antagonism. The effects of subtype-selective antagonists WB 4101 [2-(2-6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride] and 5-methylurapidil on agonist-induced contractions were also examined. WB 4101 competitively antagonized agonist-induced contractions; pA2 values were 8.13+/-0.10 and 8.10+/-0.03 against phenylephrine and A 61603, respectively. Corresponding values for 5-methylurapidil were 8.28+/-0.17 and 7.93+/-0.02 against phenylephrine and A 61603, respectively. Tamsulosin and Rec 15/2739 [(8-3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylcarbamoyl)-3-methy l-4-oxo-2-phenyl-4H-1-benzopyran dihydrochloride] also antagonized phenylephrine- and A 61603-induced contractions with pA2 values of 9.38+/-0.13 and 9.18+/-0.06 (tamsulosin) and 8.41+/-0.12 and 8.34+/-0.11 (Rec 15/2739) against phenylephrine and A 61603, respectively. HV 723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxyethyl) -amino)-propyl)benzene-aceto-nitrile) fumarate) competitively antagonized phenylephrine-induced contractions with a pA2 value of 8.57+/-0.06. Chloroethylclonidine (CEC; 10(-4) M) shifted phenylephrine and A 61603 concentration-response curves to the right, reducing their potencies approximately two- to threefold, while the maximum response was reduced by 8% in both cases. It was therefore concluded that contractions of the rabbit spleen induced by alpha1-adrenergic agonists were mediated predominantly by a relatively CEC-insensitive alpha1-adrenoceptor subtype, possibly the alpha1L-subtype.
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Safat.
M A
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Oriowo
D000097:Acetonitriles / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification* / Q000187:drug effects; D013154:Spleen / Q000187:drug effects* / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
C094643:A 61603; D000097:Acetonitriles; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002867:Chromones; D004146:Dioxanes; D007093:Imidazoles; C099870:Rec 15-2739; D018340:Receptors, Adrenergic, alpha-1; D013764:Tetrahydronaphthalenes; C058562:HV 723; D010656:Phenylephrine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane