We investigated the relaxant effect Of beta(2)-adrenoceptor agonist formoterol and beta(3)-adrenoceptor agonist BRL 37344 on bovine iris sphincter and ciliary muscle and measured CAMP and cGMP levels. his sphincter (n = 16) and ciliary muscle (n = 16) strips were mounted in organ baths and tested for changes in isometric tension in response to formoterol and BRL 37344. Their relaxant effects on serotonin-induced contractions in the presence or absence of metoprolol, ICI 118.551 and SR 59230A (beta(1)-, beta(2)-, beta(3)-adrenoceptor antagonist, respectively) were investigated. Their effects on CAMP and cGMP levels in iris sphincter (n = 12) and ciliary muscle (n = 12) were evaluated. Formoterol (10(-11)-10(-5) M) and BRL 37344 (10(-10)-10(-5) M) decreased the serotonine-induced contractions in a concentration-dependent manner. E-max values of formoterol were significantly higher than those of BRL 37344 in iris sphincter and ciliary muscle, with no significant change in pD(2) values. The relaxation responses by formoterol and BRL 37344 were antagonized with ICI 118.551 (10(-6) M) and SR 59230A (10(-6) M). CAMP levels of formoterol- and BRL 37344-treated tissues were significantly higher than those of the control tissues. cGMP levels of BRL 37344-treated tissues were significantly higher than those of control tissues, but this effect of BRL 37344 was less significant than its effect on CAMP levels. beta-adrenoceptor relaxation responses in bovine iris sphincter and ciliary muscle are mediated by a mixed population Of beta(2)- and beta(3)-adrenoceptor subtypes, with a predominant contribution of cAMP. Potency of formoterol and BRL 37344 was similar, but efficacy of formoterol was better than BRL 37344. (c) 2006 Elsevier B.V. All rights reserved.