THE CA2-K 8644 INDUCES CENTRAL RESPIRATORY DEPRESSION IN CATS, AN EFFECT BLOCKED BY NALOXONE( CHANNEL AGONIST BAY)

We analyzed the respiratory effects induced by the Ca2+ channel agonis t Bay K 8644 and its enantiomers, Bay R 5417 and Bay R 4407, applied t o the ventral medullary surface of cats. Bay K 8644 (10 to 100 mug) an d Bay R 5417 (50 to 200 mug) elicited a dose-dependent respiratory dep ression. Naloxone (0.1 mg/kg), but not D-naloxone, reversed these effe cts, indicating that an endogenous opioid mechanism was involved. Bay R 4407 (100 mug) was ineffective. The respiratory depressant effects i nduced by Bay K 8644 and its (-) enantiomer were a consequence of thei r agonist properties on the L-type Ca2+ channel, since (1) the activit y of Bay K 8644 was stereospecific, and (2) nimodipine prevented the e ffect. We suggest that potent activation of Ca2+ channels or other mec hanisms by high doses of Ca2+ agonists elicits the release of endogeno us opioid peptides in medullary respiration-related structures.