Abstract

Tyramine in concentrations (3 x 10^-7-3 x 10^-8 g/ml) which did not contract reserpine-pretreated aortic strips increased their amplitude of response to low concentrations of histamine. The potentiation was equivalent to more than a doubling of the agonist concentration in the muscle chambers. Similar effects were observed in untreated strips when the release of endogenous catecholamines by tyramine was prevented with cocaine (1 x 10^-5 g/ml). The responses to histamine and the effects of tyramine were blocked by the antihistamine d-chlorpheniramine but not by the alpha receptor antagonist phentolamine, thus ruling out the possibility that the direct contractile effects of tyramine were enhanced by histamine. The augmentation produced by tyramine was greater after inhibition of diamine oxidase suggesting that this amine blocked an alternate pathway of histamine degradation. The enhancement of respouses to histamine produced by known inhibitors of imidazole-N-methyltransferase, amodiaquin and quinidine, was abolished in the presence of tyramine (3 x 10^-6 g/ml). Similarly, tyramine produced only a slight additional increment in response amplitude in the presence of known inhibitors of N-methylation. Studies with the oil immersion technique, to eliminate diffusion of agonist into the bathing medium, revealed that tyramine (3 x l0^-6 g/ml) significantly slowed the relaxation (termination of action) of histamine contracted strips in oil after inhibition of diamine oxidase. These results indicate that tyranune enhances responses to histamine in aortic strips by decreasing the rate of its inactivation by N-methylation.