Release of [3H]noradrenaline by alpha 1-adrenoceptor agonists

Mouse isolated vas deferens preincubated with [3-H]noradrenaline was superfused and the effect of alpha 1-adrenoceptor agonists was studied on the release of total radioactivity ([3H]noradrenaline + 3H-metabolites) and [3H]noradrenaline. Reverse phase high pressure liquid chromatography (HPLC) combined with scintillation spectrometry was used to separate [3H]noradrenaline from its metabolites. Among the alpha 1-adrenoceptor agonists (1-phenylephrine, ST-587(2-(2(1)-chloro-5-trifluoromethyl phenylamino)-imidazole), (-)-amidephrine, methoxamine, cirazoline and 1-noradrenaline) studied 1-phenylephrine, ST-587 and 1-noradrenaline were capable of releasing 3H-noradrenaline. The effect of noradrenaline was stereospecific. As determined by HPLC combined with scintillation spectrometry the release of total radioactivity in response to 1-noradrenaline is mainly due to [3H]noradrenaline. It is suggested that 1-noradrenaline, 1-phenylephrine, and ST-587 in addition to their direct effect on different receptors they also have indirect action through the release of noradrenaline which might be partly involved in the pharmacological responses. The mechanisms whereby 1-noradrenaline and 1-phenylephrine release noradrenaline would appear to involve a saturable Ca-independent and a cocaine and temperature sensitive process. On the basis of our findings among the alpha 1-adrenoceptor agonists studied (-)-amidephrine, methoxamine and cirazoline is a better choice than 1-phenylephrine or ST-587 for selective stimulation of postjunctional alpha 1-adrenoceptors, they do not release noradrenaline.