CHARACTERIZATION, LOCALIZATION AND DISTRIBUTION OF alpha 1 ADRENOCEPTOR SUBTYPE IN MALE RABBIT URETHRA

Abstract

Purpose The subtype specificity, localization and distribution of urethral alpha 1-adrenoceptors were studied in the male rabbit urethra. Materials and Methods The properties of the urethral alpha 1-adrenoceptors were investigated using radioligand receptor binding and light microscopic autoradiography with [( 125) I]iodo-2-[b-(4-hydroxyphenyl)-ethylaminomethyl]tetralone (HEAT), and immunohistochemistry with monoclonal anti-alpha smooth muscle actin and anti-alpha sarcomeric actin antibodies. Results Saturation experiments with [( 125) I]HEAT demonstrated the presence of significant amounts of a single high affinity binding site for alpha 1 adrenoceptors in the male rabbit urethra. The pharmacological profile of the alpha 1 adrenoceptors in rabbit urethra, determined by inhibition experiments with subtype selective alpha 1 adrenoceptor antagonists, was characterized by the following rank order of potency of inhibition constants (K i values): prazosin <or= to WB 4101 < spiperone < 5-methylurapidil < BMY 7378. The pKi values for the rabbit urethra were correlated with the pKi values for rat spleen, submaxillary glands, and vas deferens and for those reported for cloned alpha 1d receptors with correlation coefficients of 0.68, 0.929, 0.909, and 0.523, respectively. Conclusions The pharmacological characterization demonstrates the predominance of alpha 1A or alpha 1A + alpha 1B adrenoceptor subtype(s) in male rabbit urethral smooth muscle. Furthermore, the autoradiographic and immunohistochemical studies show a heterogeneous distribution of alpha 1 adrenoceptors along the longitudinal axis of the urethra, within the smooth muscle fibers, with the receptors being localized more densely in the proximal than in the distal urethra.