Endothelin ETB Receptors Are Involved in the Relaxation to the Pig Urinary Bladder neck

Abstract

The involvement of endothelin receptors in the contraction of the lower urinary tract smooth muscle is well established. There is scarce information, however, about endothelin receptors mediating relaxation of the bladder outlet region. The current study investigates the possible existence of endothelin ET(B) receptors involved in the relaxation of pig bladder neck. ET(B) receptor expression was determined by immunohistochemistry and urothelium-denuded bladder neck strips were mounted in organ baths for isometric force recording. ET(B) -immunoreactivity (ET(B) -IR) was observed within nerve fibers among smooth muscle bundles and urothelium. BQ3020 (0.01-300 nM), an ET(B) receptor agonist, produced concentration-dependent relaxations which were reduced by BQ788, an ET(B) receptor antagonist, and by inhibitors of protein kinase A (PKA) and large (BK(Ca) )- or small (SK(Ca) )-conductance Ca(2+) -activated K(+) channels. Pretreatment with BK(Ca) or SK(Ca) channel inhibitors plus PKA blocking did not cause further inhibition compared with that exerted by inhibiting BK(Ca) or SK(Ca) channels only. BQ3020-induced relaxation was not modified by blockade of either nitric oxide (NO) synthase, guanylyl cyclase, cyclooxygenase (COX) or of intermediate-conductance Ca(2+) -activated-(IK(Ca) ), ATP-dependent-(K(ATP) ), or voltage-gated-(K(v) ) K(+) channels. Under non-adrenergic non-cholinergic (NANC) conditions, electrical field stimulation (0.5-16 Hz) evoked frequency-dependent relaxations, which were reduced by BQ788 and potentiated by threshold concentrations of BQ3020. These results suggest that BQ3020 produces relaxation of the pig bladder neck via activation of muscle endothelin ET(B) receptors, NO/cGMP- and COX-independent-, cAMP-PKA pathway-dependent-mechanisms, and involving BK(Ca) and SK(Ca) channel activation. ET(B) receptors are also involved in the NANC inhibitory neurotransmission.