Effects in vitro and in vivo by apomorphine in the rat corpus cavernosum.
The study was performed to clarify if apomorphine at the level of the rat corpus cavernosum can produce erectile responses or interfere with nerve-induced penile erection. Apomorphine (10(-9)-10(-4) M) exhibited a 10-fold higher potency to relax phenylephrine (Phe)- than endothelin-1 (ET-1)-induced contractions. Relaxant effects of apomorphine in Phe-activated corpus cavernosum did not change tissue levels of cyclic nucleotides, and were unaffected by inhibition of the synthesis of nitric oxide, or by inhibition of the soluble guanylate cyclase. Relaxations by apomorphine of ET-1-contracted rat corpus cavernosum were not influenced by alpha2-adrenoceptor blockade (yohimbine, 10(-7) M), or by the dopamine D1-like receptor antagonist SCH 23390 (10(-6) M). Clozapine (10(-6) M), a proposed dopamine D2-like receptor antagonist, partly reduced apomorphine-induced relaxations, and significantly altered the -log IC50 value for apomorphine. Nerve-induced contractions of the rat corpus cavernosum were attenuated by apomorphine in a concentration-dependent and biphasic manner. Yohimbine (10(-7) M) abolished the biphasic concentration-response pattern. SCH 23390 (10(-6) M) attenuated the inhibitory effects of apomorphine on contractions, and significantly altered the -log IC50 value for the compound. In anesthetized rats (50 mg kg(-1) pentobarbital sodium, 10 mg kg(-1) ketamine), intracavernous apomorphine (100, 300, or 1000 nmol) did not have effects on basal cavernous pressure under resting conditions, and did not affect filling or emptying rates, or peak pressures of the rat corpus cavernosum during submaximal activation of the cavernous nerve. In awake rats, apomorphine produced a maximal number of erections at 300 nmol kg(-1). In the rat isolated corpus cavernosum, pre- and postjunctional effects of apomorphine appear to involve dopamine D1- and D2-like receptors, as well as alpha-adrenoceptors. At relevant systemic doses of apomorphine, peripheral effects of the compound are unlikely to contribute to its proerectile effects in rats.
Matsumoto
Kenshi
K
Department of Clinical and Experimental Pharmacology, Lund University Hospital, Lund S-221 85, Sweden.
Yoshida
Masaki
M
Andersson
Karl-Erik
KE
Hedlund
Petter
P
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000494:pharmacology; D006151:Guanosine / Q000378:metabolism; D066298:In Vitro Techniques; D007267:Injections; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009213:Myography; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014851:Wakefulness / Q000502:physiology
D018491:Dopamine Agonists; D019332:Endothelin-1; D006151:Guanosine; D000242:Cyclic AMP; D006152:Cyclic GMP; D001058:Apomorphine