d-Tubocurarine as a dopaminergic antagonist in the rabbit ear artery

d-Tubocurarine has been reported to inhibit the action of dopamine on mollusc neurons. The purpose of the present study was to determine whether or not d-tubocurarine acts as an antagonist on mammalian dopamine receptors. The isolated, perfused rabbit ear artery was the experimental preparation used. In this preparation dopamine and apomorphine produced concentration-dependent inhibition of the response to electrical field stimulation of the periarterial sympathetic nerves. d-Tubocurarine antagonized the inhibitory effect of dopamine and apomorphine in a competitive manner. The calculated dissociation constants for d-tubocurarine acting against dopamine and apomorphine were 1.9 +/- 0.6 microM and 1.7 +/- 0.5 microM, respectively. d-Tubocurarine (1-100 microM), by itself, did not affect the response of the artery to sympathetic nerve stimulation. Other nicotinic antagonists hexamethonium, pancuronium and mecamylamine did not affect the dopamine action. These results suggest that d-tubocurarine could attenuate the therapeutic benefit of dopamine if both of these drugs are administered concomitantly.