Cyclic Adenosine Monophosphate Production and Contractile Response Induced by Beta-Adrenoceptor Subtypes in Rabbit Urinary Bladder Smooth Muscle

Abstract

The spontaneous contractile force of muscle strips isolated from male rabbit urinary bladder dome (detrusor) and base (trigonal muscle) was dose dependently inhibited by isoproterenol, a non-specific beta-adrenoceptor agonist. The relaxant response to 10^––6M isoproterenol in the detrusor muscle was completely blocked by butoxamine (10^––4M), a selective beta-2-antagonist, and by propranolol (10^––6M), a non-specific beta-antagonist, but not by metopronol (10^––6 to 10^––4M), a selective beta-1-antagonist. Relaxation of trigonal muscle induced by 10^––6M isoproterenol was inhibited 30% by metoprolol (10^––5M), 70% by butoxamine (10^––4M), and 100% by propranolol (10^––6M). Terbutaline, a selective beta-2-adrenoceptor agonist, also caused dose dependently a relaxant response in detrusor and trigonal muscle. The maximum relaxant responses to isoproterenol and terbutaline were significantly greater in detrusor than in trigonal muscle. Dobutamine, a relatively specific beta-1-adrenoceptor agonist, caused a small but significant relaxant response in trigonal, but no change in detrusor muscle. In trigonal muscle the relaxant response to dobutamine was less than that to terbutaline. Cyclic adenosine monophosphate accumulation in detrusor did not significantly increase after administration of dobutamine, but significantly increased after administration of terbutaline. On the other hand, not only terbutaline, but also dobutamine, markedly increased cyclic adenosine monophosphate accumulation in trigonal muscle. These findings are consistent with the detrusor having a greater density of beta-adrenoceptors than trigonal muscle and with the relaxant responses to beta-adrenoceptors being mediated by the beta-2-subtype in the detrusor and by both beta-1 – and beta-2-subtypes in trigonal muscle of the rabbit through cyclic adenosine monophosphate accumulation.

Regional Difference in Functional Roles of cAMP and cGMP in Lower Urinary Tract Smooth Muscle Contractility

“…These results reveal that the relaxation responses with isoproterenol in rabbit lower urinary tract smooth muscles may be me diated by cAMP. These results are compatible with pre vious reports [5,6], Levin et al [7] reported that isopro terenol produced a significant increase in cAMP levels in rabbit urinary bladder dome but not in bladder base. We have reported that rabbit urinary bladder dome, base and urethra contain some amount of (3-adrenoceptors [8], Our results are consistent with the data of receptor assay [8].…”

β-Adrenoceptor Subtypes in the Detrusor of Guinea-Pig Urinary Bladder

“…Indeed, using a pharmacological tool like butoxamine, another selective P2-adrenoceptor antagonist. Morita et al [10] showed that the relaxant response to 1 \iM isoprotere nol in the rabbit bladder detrusor was com pletely blocked. This finding from the con tractile studies is corroborated by the radioligand-binding results of Anderson and Marks [11] and Levin et al [ 12], in which either only a minor fraction (13-23%) or a quantity be low the level of detection of Pi-adrenoceptors was found in the rabbit bladder detrusor.…”

Effects of various phosphodiesterase-inhibitors, forskolin, and sodium nitroprusside on porcine detrusor smooth muscle tonic responses to muscarinergic stimulation and cyclic nucleotide levels in vitro

“…It is well known that an increase in cyclic nucleotide levels in smooth muscle results in relaxation of the muscle through decreases in cytosolic calcium concentrations [Lincoln and Cornwell, 19911. While adenylate cyclase activation, CAMP accumulation, and smooth muscle relaxation has been linked to P,-adrenergic stimulation [Morita et al, 1990[Morita et al, , 1992Lincoln and Cornwell, 1991;Persson and Andersson, 19941, the role of the guanylate cyclase-cGMP pathway and its modulation by autonomic receptors is less clear in the detrusor smooth muscle [Anderson 1990[Anderson , 1993Persson and Anderson, 19941. Recently, a number of endogenous hormones and other regulatory substances have been identified which can induce smooth muscle relaxation via increases of intracellular cyclic nucleotide levels, however, their precise role in regulation of detrusor contractility remains to be established [Anderson, 19931. Since cyclic nucleotides are degraded by phoshodiesterase enzymes, considerable attention has been focused over the last few years on the therapeutic potential of isoenzyme-selective PDE-inhibitors to influence the tone of smooth muscle organs in vivo.…”

“…Cyclic nucleotides are synthetized from their respective nucleoside triphosphates following activation of adenylate or guanylate cyclases, respectively [Lincoln and Cornwell, 19911. While adenylate cyclase activation, CAMP accumulation, and smooth muscle relaxation has been linked to P,-adrenergic stimulation [Morita et al, 1990[Morita et al, , 1992Lincoln and Cornwell, 1991;Persson and Andersson 19941, the role of the guanylate cyclase-cGMP pathway and its modulation by autonomic receptors is less clear in the detrusor smooth muscle [Anderson 1990[Anderson , 1993Persson and Andersson, 19941. Inactivation of cyclic nucleotides occurs via hydrolyzation by a group of enzymes called phosphodiesterases (PDEs). Currently, five families of PDEs can be distinguished from their substrate specificity, chromatographic properties, and susceptibility to inactivation by specific inhibitors [Beavo, 19901.…”