POSSIBLE ROLE OF THE ALPHA-ADRENOCEPTOR IN THE MODULATION OF ADRENERGIC COTRANSMISSION IN THE GUINEA-PIG VAS-DEFERENS

We observed the effects of prazosin (10(-8) - 10(-5) M) on noradrenaline (NA) and dihydroxyphenylethylene glycol (DOPEG) overflow, and on excitatory junction potentials (e.j.p.s) before and after pretreatment with yohimbine, using high pressure liquid chromatography (HPLC), double sucrose-gap and microelectrode methods. Prazosin and yohimbine (10(-8) - 10(-5) M) dose-dependently increased the resting and stimulated overflow of DOPEG, or the stimulated overflow of NA. After pretreatment with yohimbine (10(-7) M) or prazosin (10(-7) M), additional application of prazosin or yohimbine, respectively, further increased the stimulated NA overflow. Yohimbine (10(-7) M), but not prazosin (10(-7) M), significantly increased the amplitude of the e.j.p. without changing the resting membrane potential or input membrane resistance of the smooth muscle cells. Both prazosin (10(-7) M) and yohimbine (10(-7) M) significantly enhanced the growth curve (facilitation phenomenon) of e.j.p.s evoked by repetitive stimulation at 0.2 or 0.5 Hz. Each of the drugs produced an additional facilitatory effect on e.j.p.s which had been facilitated by pretreatment of the tissue with the other drug. During prolonged treatment of the vasa with alpha,beta-methylene adenosine 5'-triphosphate (alpha-beta-mATP), single or repetitive field stimulation evoked small and slow e.j.p.s (s.s.e.j.p.s) which were sensitive to tetrodotoxin (10(-7) M) or guanethidine (10(-6) M), but not to the P2y- purinoceptor blocking agent, reactive blue 2 (10(-5) M). E.j.p.s recorded from reserpinized vasa showed enhanced facilitation at stimulus frequencies of 0.2 and 0.5 Hz. Neither prazosin nor yohimbine (up to 10(-6) M) had any effect on the e.j.p. amplitude or facilitation after reserpinization. The present results may indicate that prejunctional alpha-1- and alpha-2-adrenoceptors both contribute to the negative feedback control of NA and ATP release from sympathetic nerve terminals in the guinea-pig vas deferens.