Examination of the paradoxical lack of responsiveness of the guinea-pig vas deferens to tyramine.

Abstract

1. The isolated superfused vas deferens from the guinea-pig was more sensitive to the contractile action of noradrenaline than that from the rat. Tyramine had about 10% of the potency of noradrenaline on the rat vas deferens, but had no contractile activity on the guinea-pig vas deferens (potency less than 0.1% of noradrenaline). 2. The response of the guinea-pig vas deferens to noradrenaline was not affected by tyramine in a concentration that produced a clear contractile response of the rat vas deferens. 3. Noradrenaline and tyramine released less radioactivity from guinea-pig than from rat vasa deferentia in which noradrenergic transmitter stores had been labelled with 3H-noradrenaline. In vasa deferentia from either species, tyramine released less radioactivity than noradrenaline. 4. Pretreatment with the monoamine oxidase inhibitor iproniazid increased the amount of radioactivity released by tyramine from vasa deferentia of both species, increased the contractile response of the rat vas deferens to tyramine, and resulted in the appearance of a contractile response to tyramine in the guinea-pig vas deferens. 5. alpha-methyltyramine, which is not a substrate for monoamine oxidase, had about the same potency as tyramine in releasing radioactivity from vasa deferentia of both species, and in contracting the rat vas deferens, but was virtually without contractile activity on the guinea-pig vas deferens. 6. Pretreatment with iproniazid resulted in the appearance of a contractile response to alpha-methyltyramine in the guinea-pig vas deferens. 7. Pretreatment with iproniazid resulted in change in the composition of the radioactivity released by tyramine, with an increase in the proportion of noradrenaline and a decrease in the proportion of deaminated products. There was also an increase in the amount of endogenous noradrenaline released by tyramine. 8. It was concluded that the main factor accounting for the lack of reactivity of the guinea-pig vas deferens to tyramine is intraneuronal metabolism of the noradrenaline displaced by it.