alpha(1)-adrenoceptor subtypes mediating contractions of the rat mesenteric artery

The alpha(1)-adrenoceptor subtype(s) mediating contractions of the rat mese nteric artery were investigated using the agonists methoxamine, cirazoline, P7480 (N-(4-pyridinyl)-1 H-indol-1-amine) and subtype-selective antagonist s including BMY 7378 (8-(-2(-4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-aza spiro dihydrochloride). pA(2) or apparent pK(B) values of antagonists again st methoxamine contractions correlated best with its pK(i) values at the cl oned alpha(1b)-(0.88), with cirazoline, antagonists affinities correlated e qually well with those at alpha(1a)-(0.79) or the alpha(1b)-(0.81) while wi th P7480 antagonist affinities correlated best with the alpha(1d)-adrenocep tor subtype (0.94). The low affinity estimate for 5-methylurapidil (7.5) ag ainst the alpha(1a)-selective cirazoline suggests an alpha(1A)-subtype medi ating contraction is unlikely. Shallow Schild plot slopes of subtype select ive antagonists against all three agonists are consistent with heterogeneit y of alpha(1)-adrenoceptors. P7480 (putative alpha(1D)-adrenoceptor-selecti ve) acts primarily at this subtype and at another which is more likely to b e an alpha(1B)- than an alpha(1A)-adrenoceptor. The results with both agoni sts and antagonists are consistent with contractions of the rat mesenteric artery being mediated via the alpha(1D)- and possibly alpha(1B)-adrenocepto r. (C) 2000 Elsevier Science B.V. All rights reserved.