The Ca2+ channel agonist Bay K 8644 induces central respiratory depression in cats, an effect blocked by naloxone.
We analyzed the respiratory effects induced by the Ca2+ channel agonist Bay K 8644 and its enantiomers, Bay R 5417 and Bay R 4407, applied to the ventral medullary surface of cats. Bay K 8644 (10 to 100 micrograms) and Bay R 5417 (50 to 200 micrograms) elicited a dose-dependent respiratory depression. Naloxone (0.1 mg/kg), but not D-naloxone, reversed these effects, indicating that an endogenous opioid mechanism was involved. Bay R 4407 (100 micrograms) was ineffective. The respiratory depressant effects induced by Bay K 8644 and its (-) enantiomer were a consequence of their agonist properties on the L-type Ca2+ channel, since (1) the activity of Bay K 8644 was stereospecific, and (2) nimodipine prevented the effect. We suggest that potent activation of Ca2+ channels or other mechanisms by high doses of Ca2+ agonists elicits the release of endogenous opioid peptides in medullary respiration-related structures.
Ruiz
F
F
Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, Spain.
Dierssen
M
M
Flórez
J
J
Hurlé
M A
MA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002415:Cats; D004347:Drug Interactions; D005260:Female; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects*; D013237:Stereoisomerism
D015220:Calcium Channels; D009270:Naloxone; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester