Role of calcium channels and adenylate cyclase in the PACAP-induced adrenal catecholamine secretion.
We elucidated the functional contribution of voltage-dependent calcium channels (VDCCs) and adenylate cyclase to epinephrine (Epi) and norepinephrine (NE) secretion induced by pituitary adenylate cyclase-activating polypeptide (PACAP) in the isolated perfused rat adrenal gland. PACAP increased Epi and NE output, which was inhibited by perfusion with calcium-free solution or by nifedipine, an L-type VDCC blocker. However, the PACAP-induced responses were resistant to omega-conotoxin GVIA, an N-type VDCC blocker, or omega-conotoxin MVIIC, a P/Q-type VDCC blocker. MDL-12330A, an adenylate cyclase inhibitor, inhibited the PACAP-induced increase in Epi, but not NE, output. Treatment with nifedipine and MDL-12330A caused additive inhibition of the PACAP-induced catecholamine responses. These results suggest that opening of L-type VDCCs is responsible for adrenal catecholamine secretion induced by PACAP and that activation of adenylate cyclase is involved in the PACAP-induced Epi, but not NE, secretion. These pathways may act independently of each other.
Fukushima
Y
Y
Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan.
Nagayama
T
T
Kawashima
H
H
Hikichi
H
H
Yoshida
M
M
Suzuki-Kusaba
M
M
Hisa
H
H
Kimura
T
T
Satoh
S
S
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002395:Catecholamines; D007097:Imines; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; C014925:RMI 12330A; D020866:omega-Conotoxin GVIA; D000262:Adenylyl Cyclases; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine