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Effects of T‐type calcium channel blockers and thalidomide on contractions of rat vas deferens
Author(s) -
Seto Sai Wang,
Docherty James R.
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00600.x
Subject(s) - vas deferens , mibefradil , nifedipine , calcium channel , endocrinology , voltage dependent calcium channel , medicine , t type calcium channel , stimulation , contraction (grammar) , calcium , chemistry
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 µM) 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 µM) inhibited contractions in epididymal (55 ± 4% of control, n = 17) but not in prostatic portions of rat vas deferens. Thalidomide (10–100 µM) 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.