Prejunctional facilitatory α1‐adrenoceptors in the rat urinary bladder

Abstract

1. The effect of activation of alpha 1-adrenoceptors on acetylcholine (ACh) release and neurally evoked contractile responses induced by electrical field stimulation was investigated in smooth muscle strips from the rat urinary bladder. 2. Neurogenic contractions were facilitated by the alpha 1-adrenoceptor agonists, phenylephrine (PE) (2-128 microM) and methoxamine (2-128 microM) in a dose-dependent manner. These agents also increased small amplitude spontaneous contractions of bladder strips and in 10% of strips increased basal tone. However, contractions elicited by exogenous ACh (1-10 microM) were not affected by alpha 1-agonists. 3. The magnitude of the PE facilitation was higher at lower frequencies (1-5 Hz) or at submaximal intensities of stimulation and at lower Ca2+ concentrations (0.5-1 mM). The selective alpha 1-adrenoceptor antagonist, terazosin (TRZ) (0.05-1 microM), competitively inhibited (pA2 value: 8.6) the PE facilitation of the neurally evoked contractions but not the PE induced increase of spontaneous contractions. 4. [3H]-noradrenaline (NA) and [14C]-ACh release evoked by electrical field stimulation were increased (140% and 173%, respectively) by 2 microM PE. TRZ (0.05-0.1 microM) blocked the PE facilitation of ACh release but not the facilitation of NA release. TRZ alone did not alter the release of ACh or NA nor the amplitude of the neurogenic contractions. 5. PE (2 microM) did not alter the basal release of ACh but did increase (by 180%) the basal release of NA. Desipramine (2 microM) blocked this effect of PE and also the PE-facilitation of evoked ACh and NA release. 6. It is concluded that cholinergic terminals in the rat urinary bladder exhibit alpha 1-adrenoceptors which can facilitate the release of transmitter. However, under the conditions of our experiments it appears that cholinergic transmission is not modulated by alpha 1 adrenergic mechanisms. Further studies are necessary to determine whether these receptors can be activated by endogenous noradrenaline released within the bladder.