Premium
Pharmacological analysis of the effects of Bay K 8644 and organic calcium antagonists on the mouse isolated distal colon
Author(s) -
Fontaine Jeanine,
Lebrun Philippe
Publication year - 1988
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.1476-5381.1988.tb11639.x
Subject(s) - depolarization , verapamil , nifedipine , chemistry , tetrodotoxin , egta , phentolamine , medicine , endocrinology , calcium , biology , propranolol
1 Bay K 8644 (10 −8 to 10 −6 m ) induced concentration‐related contractions of the longitudinal muscle of the mouse distal colon. The maximal responses were enhanced and the EC 50 was lowered in the presence of tetrodotoxin (TTX; 1.5 × 10 −7 m ). The responses were not affected by atropine (10 −7 m ), mepyramine (2.5 × 10 −7 m ), methysergide (5 × 10 −7 m ), propranolol (10 −6 m ), phentolamine (10 −6 m ) or naloxone (4 × 10 −7 m ). By contrast, the contractile responses were inhibited by Ca 2+ entry blockers (verapamil, nifedipine) and abolished in Ca 2+ ‐free EGTA solution. These observations indicate that the contractile effects of Bay K 8644 are dependent on its ability to promote Ca 2+ influx. 2 At 10 −4 m , Bay K 8644 provoked a slow relaxation of the preparation. Moreover, from 10 −5 m , Bay K 8644 markedly reduced the contractile responses to ACh and K + depolarization. These inhibitory effects were comparable with those produced by nifedipine. Such data suggest that, at high concentrations, Bay K 8644 could act in part as a dihydropyridine Ca 2+ channel antagonist. 3 Bay K 8644 (10 −9 m ) preferentially enhanced, while nifedipine (10 −10 to 10 −8 m ) as well as verapamil (3 × 10 −9 to 10 −6 m ) preferentially inhibited, the tonic component of the contractile response evoked by K + depolarizing solution. This may indicate that different populations of voltage‐sensitive Ca 2+ channels are involved in the biphasic response to K + depolarization. 4 The biphasic contractile activity induced by ACh was barely enhanced by Bay K 8644 (10 −9 m ) and was less sensitive to Ca 2+ entry blockers than the responses to KCl. These findings are discussed in terms of receptor‐operated channels and mobilization of bound calcium.