Release of noradrenaline by labetalol in the rat anococcygeus muscle.

The effects of labetalol on the accumulation and spontaneous release of (--)-[3H]noradrenaline, and on contractile responses to exogenously applied (--)-noradrenaline were studied in the isolated anococcygeus muscle of the rat. 1. Labetalol (3 x 10(-7)--10(-4)M) inhibited the accumulation of (--)-[3H]noradrenaline. 2. Labetalol (10(-6)--10(-4)M) and guanethidine (6 x 10(-6) M) increased the spontaneous release of [3H] following incubation of the muscle with (--)-[3H]noradrenaline. Nortriptyline (10(-6) M) had no effect on the spontaneous release of [3H], antagonised the increased release of [3H] produced by 6 x 10(-6) M guanethidine but not that observed with 10(-5) M labetalol. Labetalol (5 x 10(-6) M) markedly increased the loss of tritiated deminated metabolites with little change in the loss of (--)-[3H]noradrenaline. 3. Labetalol (10(-7)--10(-5)M), alone or in the presence of 10(-6) M nortriptyline, had no effect on contractile responses to (--)-noradrenaline. 4. Following pretreatment with 6-hydroxydopamine (10(-3)M for 3 h) to deplete endogenous noradrenaline stores, labetalol (10(-7)--10(-5) M) inhibited responses to exogenously applied (--)-noradrenaline. 5. These results suggest that, in the rat anococcygeus muscle, labetalol is a noradrenaline releasing agent and an alpha-adrenoceptor antogonist.