Differential effects of drugs interacting with autonomic transmitters on responses of rat vas deferens to field stimulation

1 Frequency-response curves (0.1-30 Hz) were obtained in the epididymal por tion of rat vas deferens. At low frequencies (0.1-1 Hz), the parameters eva luated were the first twitch and the fourth twitch at each frequency. The r esponses to trains of stimuli at intermediate (2-5 Hz) and high (10-30 Hz) frequencies were biphasic consisting of phase I (the first rapid phase of t etanus) and of phase II (the secondary slowly developing one). 2 Prazosin inhibited the first and the fourth twitch but not when the frequ ency was <1 Hz. Suramin inhibited the first twitch while substantially depr essing the fourth one. The combination of prazosin and suramin almost compl etely abolished all the twitches evoked by a train of stimuli at low freque ncies. Nifedipine left almost unaltered the first twitch while markedly dep ressing the fourth one, especially at relatively high frequency (1 Hz). Ver apamil was devoid of any inhibitory action. Papaverine depressed the first twitch while only at the highest concentration used (1x10-4 M) markedly inh ibited the fourth one. Chloroethylclonidine (CEC) depressed the first twitc h and increased the fourth. 3 When intermediate (2-5 Hz) and high (10-30 Hz) frequencies are considered , prazosin and suramin partially inhibited both phase I and phase II, while in combination they almost completely abolished both phases. Nifedipine an d verapamil selectively suppressed phase II, leaving phase I unaffected. Pa paverine completely abolished both phase I and phase II. CEC was able to co mpletely abolish phase I but increased phase II. 4 These results suggest that the response to the first twitch of a train at low frequency is prevailingly noradrenergic, prazosin-sensitive, while whe n the twitches are close enough (i.e. at 1 Hz) a summation of stimuli takes place and a predominant purinergic component, both suramin- and nifedipine -sensitive, becomes evident. 5 At high frequencies, both phases are due to the concomitant release of no radrenaline and adenosine triphosphate (ATP). The noradrenergic component o f phase I is nifedipine-insensitive and CEC-sensitive, resembling the pharm acological profile of the endogenously released noradrenaline by single pul se, while that of phase II, nifedipine-sensitive and CEC-insensitive, is si milar to that produced by exogenously applied noradrenaline.