FUNCTIONAL-CHARACTERIZATION OF ALPHA(1)-ADRENOCEPTOR SUBTYPES IN THE RABBIT SPLEEN

Phenylephrine and -[5-(4,5-dihydro-1H-imidazol-2yl)-2-hydroxy-5,6,7, 8 -tetrahydronaphthalen-1-yl] methanesulphonamide hydrobromide (A 61603) evoked concentration-dependent contractions of the rabbit spleen. The se contractions were antagonized by prazosin (10(-8)-10(-7) M) with pA (2) 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 wer e not significantly (P>0.05) different from 1.0, indicating competitiv e antagonism. The effects of subtype-selective antagonists WE 4101 dim ethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride] acid 5- methylurapidil on agonist-induced contractions were also examined. WB 4101 competitively antagonized agonist-induced contractions; pA(2) val ues 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 perazinyl]propylcarbamoyl)-3-methyl-4-oxo-2 -phenyl 4H-1-benzopyran dihydrochloride] also antagonized phenylephrin e- and A 61603-induced contractions with pA(2) values of 9.38+/-0.13 a nd 9.18+/-0.06 (tamsulosin) and 8.41+/-0.12 and 8.34+/-0.11 (Rec 15/27 39) against phenylephrine and A 61603, respectively. HV 723 phenoxyeth yl)-amino)-propyl)benzene-aceto-nitrile) fumarate) competitively antag onized phenylephrine-induced contractions with a pA(2) value of 8.57+/ -0.06. Chloroethylclonidine (CEC; 10(-4) M) shifted phenylephrine and A 61603 concentration-response curves to the right, reducing their pot encies approximately two- to threefold, while the maximum response was reduced by 8% in both cases. It was therefore concluded that contract ions of the rabbit spleen induced by alpha(1)-adrenergic agonists were mediated predominantly by a relatively CEC-insensitive alpha(1)-adren oceptor subtype, possibly the alpha(IL)-subtype.