Mechanism of alpha 2-adrenergic inhibition of neuroeffector transmission in the mouse vas deferens.

The process by which the activation of presynaptic alpha 2-adrenoceptors inhibits the release of noradrenaline from terminals of postganglionic sympathetic nerves was studied in the mouse isolated vas deferens. Clonidine was used as a prototypic agonist. Field stimulation-evoked excitatory junction potentials (e.j.p.s) were recorded from individual muscle cells. The e.j.p. amplitudes were taken as a measure of transmitter release. Changes in the external Ca2+ concentration from 2.5 to 1.25 or 5 mM caused corresponding changes in the size of e.j.p.s. When the normal Ca2+ concentration of the medium (2.5 mM) was substituted by equimolar quantities of Ba2+ or Sr2+, the e.j.p. amplitudes decreased considerably. Clonidine (0.3-30 nM) inhibited the nerve stimulation-evoked e.j.p. amplitudes in a concentration-dependent manner, without altering appreciably the frequency of spontaneous e.j.p.s. Procedures known to enhance Ca2+ entry into nerve terminals, like a high Ca2+ medium (Ca2+ 5 mM) or 4-aminopyridine 30 microM reduced the effect of clonidine. Repetitive nerve stimulation at 3 Hz, which is supposed to lead to an accumulation of free Ca2+ inside nerve terminals, similarly counteracted the effect of clonidine 10 nM. Whereas the alpha 2-adrenergic inhibition of the first e.j.p. in a train was unaffected, the inhibition of all successive e.j.p.s was gradually decreased. At 5 mM Ca2+ only the time-course of facilitation became faster, the decrease in alpha 2-adrenergic inhibition proceeded with the same pulse-dependent rate as at a normal external Ca2+ concentration, although from a lower initial level.(ABSTRACT TRUNCATED AT 250 WORDS)