Facilitation and inhibition by endothelin-1 of adrenal catecholamine secretion in anesthetized dogs.
We examined the participation of endothelin ET(A) and ET(B) receptors in modulation by endothelin-1 of adrenal catecholamine secretion during cholinergic activation in pentobarbital-anesthetized dogs. Drugs were infused intra-arterially into the adrenal gland. Splanchnic nerve stimulation (1 and 3 Hz) increased adrenal catecholamine output in a frequency-dependent manner. Endothelin-1 (0.2, 0.6, and 2 ng/kg/min) enhanced the catecholamine response induced by the 3-Hz nerve stimulation. Under pretreatment with an endothelin ET(A) receptor antagonist (R)-2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-m eth ylpentanoyl]amino-3-(2-pyridyl) propionic acid (FR139317) (1 microg/kg/min), endothelin-1 suppressed the 1- and 3- Hz nerve stimulation-induced catecholamine response in a dose-dependent manner. No inhibitory or facilitatory effect of endothelin-1 was observed under simultaneous pretreatment with FR139317 and an endothelin ET(B) receptor antagonist N-cis 2, 6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-met hox ycarbonyl tryptophanyl-D-norleucine (BQ-788) (1 microg/kg/min) or under pretreatment with BQ-788 alone. These results suggest that in the dog adrenal gland, endothelin-1 facilitates and inhibits adrenal catecholamine secretion during cholinergic activation by stimulating endothelin ET(A) and ET(B) receptors, respectively.
Hosokawa
A
A
Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, 980-8578, Sendai, Japan.
Nagayama
T
T
Yoshida
M
M
Suzuki-Kusaba
M
M
Hisa
H
H
Kimura
T
T
Satoh
S
S
D000311:Adrenal Glands / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D012039:Regional Blood Flow / Q000187:drug effects; D013153:Splanchnic Nerves / Q000502:physiology
D001381:Azepines; D002395:Catecholamines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C079574:FR 139317; C086539:BQ 788; D009638:Norepinephrine; D004837:Epinephrine