Effects of T-type calcium channel blockers and thalidomide on contractions of rat vas deferens.

BACKGROUND AND PURPOSE

In rat vas deferens, nerve mediated-contractions to a single electrical stimulus consist of an early purinergic and a later adrenergic component with differing sensitivities to L-type calcium channel blockers. We have investigated the effects of the T-type calcium channel blockers mibefradil and (1S, 2S)-2-[2-[[3-(1H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl cyclopropanecarboxylic dihydrochloride (NNC 55-0396) against contractions in rat vas deferens. In addition, the actions of thalidomide were examined.

EXPERIMENTAL APPROACH

Prostatic and epididymal portions of rat vas deferens were stimulated with a single electrical stimulus every 5 min, and mouse whole vas deferens was stimulated with 40 pulses at 10 Hz every 5 min.

KEY RESULTS

Both mibefradil and NNC 55-0396 (100 microM) produced inhibition of contractions of epididymal portions (42 +/- 13%, n= 7, and 43 +/- 4%, n= 15, of control respectively). However, both agents produced small inhibitions of responses in prostatic portions, presumably by L-type calcium channel block. Thalidomide (100 microM) inhibited contractions in epididymal (55 +/- 4% of control, n= 17) but not in prostatic portions of rat vas deferens. Thalidomide (10-100 microM) also inhibited contractions in mouse vas deferens.

CONCLUSIONS AND IMPLICATIONS

The T-type calcium channel blockers mibefradil and NNC 55-0396 block particularly the adrenoceptor-mediated, nifedipine-resistant response to nerve stimulation in rat vas deferens, and this may suggest that this component involves T-type calcium channels. In addition, thalidomide has actions that resemble those of the T-type calcium channel blockers, in that it blocks nifedipine-resistant contractions in epididymal portions.