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


METHODS
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.


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
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.
Seto
Sai Wang
SW
Department of Physiology, Royal College of Surgeons in Ireland, Dublin, Ireland.
Docherty
James R
JR
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D003521:Cyclopropanes / Q000494:pharmacology; D004558:Electric Stimulation; D004822:Epididymis / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D020748:Mibefradil / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D003521:Cyclopropanes; D009281:Naphthalenes; C484287:NNC 55-0396; D020748:Mibefradil; D013792:Thalidomide