A direct inhibitory effect of erythromycin on rat urinary bladder smooth muscle

Erythromycin (EM) exerts a dual effect on the contractility of smooth muscl e. An excitatory effect mediated via motilin receptors is expressed mainly in the smooth muscle of the stomach and duodenum. The other, a direct inhib itory effect mediated via an unknown mechanism, has been described in guine a-pig and human gallbladder, in the longitudinal smooth muscle of the guine a-pig small intestine and in bronchial smooth muscle. In the present study, the effect of EM on the isolated urinary bladder of t he rat was examined using isometric force measurements. The muscarinic agon ist carbachol evoked contractions that were reduced by EM in a concentratio n-dependent manner; at 5 X 10(-4) M by 46% [from 1.04 +/- 0.42 gm. to 0.56 +/- 0.22 gm., (p <0.001)] and at. 10(-3) Ml by 57% [from 1.04 +/- 0.42 gm. to 0.45 +/- 0.20 gm., (p <0.001)]. The inhibitory effect of EM was not alte red by the nerve blocker tetrodotoxin. Electric field stimulation of 0.5 Hz , 1 Hz, and 2 Hz contracted the urinary bladder. Erythromycin at 5 X 10-4 M reduced the contractions evoked at 0.5 Hz by 15% [from 0.60 +/- 0.22 gm. t o 0.51 +/- 0.20 gm., (p = 0.004)] and at 10(-3) M by 23% [from 0.60 +/- 0.2 2 gm. to 0.46 +/- 0.12 gm., (p <0.001)]. Erythromycin failed to affect the contractions evoked by bradykinin, phenylephrine or substance P. It is conc luded that EM has a direct inhibitory effect on the rat urinary bladder smo oth muscle.