Inhibition by omega-conotoxin GVIA of adrenal catecholamine release in response to endogenous and exogenous acetylcholine.
Effects of the N-type voltage-dependent Ca2+ channel (VDCC) blocker, omega-conotoxin GVIA, and the L-type VDCC blockers, nifedipine and verapamil, on adrenal catecholamine release were examined in anesthetized dogs. These blockers were infused into the adrenal gland through the phrenicoabdominal artery. Splanchnic nerve stimulation at 1 and 3 Hz produced frequency-dependent increases in epinephrine and norepinephrine output determined from adrenal venous blood. Infusion of omega-conotoxin GVIA (0.4 micrograms/min) significantly inhibited the splanchnic nerve stimulation-evoked increases in epinephrine and norepinephrine output. Furthermore, increases in epinephrine and norepinephrine output induced by intraarterial injection of acetylcholine (3 micrograms) into the adrenal gland also were inhibited by omega-conotoxin GVIA (0.4 micrograms/min). Further inhibition of splanchnic nerve stimulation- or exogenous acetylcholine-induced increases in catecholamine output was observed even after the cessation of omega-conotoxin GVIA infusion. Neither nifedipine (1 microgram/min) nor verapamil (10 micrograms/min) affected the splanchnic nerve stimulation-evoked increases in catecholamine output, whereas they inhibited the exogenous acetylcholine-evoked catecholamine release. These results suggest that N-type VDCCs located in adrenal medullary cells may contribute to the release of adrenal catecholamines in response to endogenous and exogenous acetylcholine in the dog.
Department of Pharmacology, Tohoku University, Sendai, Japan.
T
T
Kimura
A
A
Takeuchi
S
S
Satoh
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D004837:Epinephrine / Q000097:blood*; D005260:Female; D007261:Infusions, Intra-Arterial; D008297:Male; D008978:Mollusk Venoms / Q000008:administration & dosage / Q000494:pharmacology; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D013153:Splanchnic Nerves / Q000187:drug effects / Q000502:physiology; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D008978:Mollusk Venoms; D010455:Peptides; D020866:omega-Conotoxin GVIA; D014700:Verapamil; D009543:Nifedipine; D000109:Acetylcholine; D009638:Norepinephrine; D004837:Epinephrine