beta2 and beta3-adrenoceptor inhibition of alpha1-adrenoceptor-stimulated Ca2+ elevation in human cultured prostatic stromal cells

Prostatic beta-adrenoceptors inhibit alpha(1)-adrenoceptor-stimulated contractility. This study examines the effects of beta-adrenoceptor stimulation upon phenylephrine-induced elevations of intracellular Ca(2+)([Ca(2+)](i)) in human cultured prostatic stromal cells, and contractility of human prostatic tissue. Human cultured prostatic stromal cells were used for [(3)H]-cAMP accumulation studies or were loaded with 5-oxazolecarboxylic acid, 2-(6-(bis(2-((acetyloxy)methoxy)-2-oxoethyl)amino)-5-(2-(2-(bis(2-((acetyloxy)methoxy)-2-oxoethyl)amino)-5-methylphenoxy)ethoxy)-2-benzofuranyl)-, (acetyloxy)methyl ester (FURA-2AM, 10 microM) for Ca(2+) imaging studies. The beta-adrenoceptor agonist isoprenaline increased the accumulation of [(3)H]-cAMP (pEC(50)+/-S.E.M. 6.58+/-0.11) in human cultured prostatic stromal cells, an effect antagonized by the beta(2)-adrenoceptor antagonist (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol (ICI 118,551), but not by the beta(1)-adrenoceptor antagonist, atenolol. Isoprenaline (3 microM), the adenylyl cyclase activator, forskolin (20 microM) and the phosphodiesterase-4 inhibitor, rolipram (10 microM) inhibited the elevation of [Ca(2+)](i) elicited by phenylephrine (20 microM). The effect of isoprenaline could be blocked by ICI 118,551 (100 nM), the adenylyl cyclase inhibitor cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine (MDL 12,330A, 20 microM) and the K(Ca) channel blocker, iberiotoxin (100 nM), but not by atenolol (1 microM) or the K(ATP) channel blocker, glibenclamide (3 microM). Agonists selective for beta(1)-(xamoterol and prenalterol), beta(2)-(procaterol and salbutamol) and beta(3)-((+/-)-(R(*), R(*))-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetic acid, BRL37344) adrenoceptors inhibited the elevation of [Ca(2+)](i) elicited by phenylephrine (20 microM) with a rank order of BRL37344> or =xamoterol> or =isoprenaline>procaterol> or =prenalterol>salbutamol...