2-Halogenoethylamines and the role of Ca²⁺ in adrenergic α-receptor activation in the rat vas deferens

The interaction of 2-halogenoethylamines and cinchocaine (CE), tetracaine (TE), diazoxide (DZE) and SKF 525A has been studied for the adrenergic responses of the rat vas deferens. Phenoxybenzamine (PB) and 2-SY28 normally produce a long lasting antagonism of this system while N,N-dimethyl-2-bromo2-phenylethylamine (DMPEA) produces a very short lived antagonism the recovery of which follows first order kinetics. Pretreatment of tissues with subthreshold concentrations of DMPEA prior to treatment with PB and 2-SY28 did not alter the degree of blockade but did significantly increase the rate of recovery of blockade from these latter agents. Analogous effects to those of DMPEA were produced by CE, TE and DZE. SKF 525A which selectively inhibits K⁺ but not NE-induced blockade lacked these effects. A model is proposed according to which 2-halogenoethylamines have at least two sites of action: one of these sites may be the NE recognition site proper and the other is a linked Ca²⁺ site activation of which is critical to excitation-contraction coupling. Implications of this model are discussed.