Actions of alpha, beta-methylene ATP and 6-hydroxydopamine on sympathetic neurotransmission in the vas deferens of the guinea-pig, rat and mouse: support for cotransmission.

alpha-Adrenoceptor antagonists (prazosin or phentolamine) reduced the contractile response to field stimulation of the isolated vasa deferentia of guinea-pig, rat and mouse. alpha, beta-Methylene ATP (alpha, beta-MeATP) reduced that portion of the contraction which was resistant to alpha-adrenoceptor blockade. alpha, beta-MeATP (1-800 microM) did not affect action potential conduction in the guinea-pig vas deferens nerves, and (up to 10 microM) did not reduce the stimulation-evoked overflow of [3H]-noradrenaline from this tissue. Spontaneous excitatory junction potentials (s.e.j.ps) in the majority of cells of guinea-pig, rat, and mouse vasa were abolished by alpha, beta-MeATP (0.1-10 microM). In a small number of cells s.e.j.ps were resistant to the actions of alpha, beta-MeATP (10 microM). Excitatory junction potentials (e.j.ps) in the majority of cells in vasa of all species studied were abolished by alpha, beta-MeATP (1-10 microM). E.j.ps elicited in some 'resistant' cells demonstrated marked facilitation characteristics. It is concluded that alpha, beta-MeATP inhibits s.e.j.ps and e.j.ps by a postjunctional action. In all species pretreatment of animals with 6-hydroxydopamine produced a marked reduction in noradrenaline (NA) content (as determined by fluorescence histochemistry) and abolished e.j.ps, findings which suggest that e.j.ps originated from sympathetic nerves. The results support the hypothesis that NA and ATP are co-transmitters in the sympathetic nerves of rodent vasa.