Effects of adrenomedullin and PAMP on adrenal catecholamine release in dogs.
We examined the effects of proadrenomedullin-derived peptides on the release of adrenal catecholamines in response to cholinergic stimuli in pentobarbital sodium-anesthetized dogs. Drugs were administered into the adrenal gland through the phrenicoabdominal artery. Splanchnic nerve stimulation (1, 2, and 3 Hz) and ACh injection (0.75, 1.5, and 3 microgram) produced frequency- or dose-dependent increases in adrenal catecholamine output. These responses were unaffected by infusion of adrenomedullin (1, 3, and 10 ng. kg-1. min-1) or its selective antagonist adrenomedullin-(22-52) (5, 15, and 50 ng. kg-1. min-1). Proadrenomedullin NH2-terminal 20 peptide (PAMP; 5, 15, and 50 ng. kg-1. min-1) suppressed both the splanchnic nerve stimulation- and ACh-induced increases in catecholamine output in a dose-dependent manner. PAMP also suppressed the catecholamine release responses to the nicotinic agonist 1, 1-dimethyl-4-phenylpiperazinium (0.5, 1, and 2 microgram) and to muscarine (0.5, 1, and 2 microgram), although the muscarine-induced response was relatively resistant to PAMP. These results suggest that PAMP, but not adrenomedullin, can act as an inhibitory regulator of adrenal catecholamine release in vivo.
Masada
K
K
Department of Pharmacology, Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan.
Nagayama
T
T
Hosokawa
A
A
Yoshida
M
M
Suzuki-Kusaba
M
M
Hisa
H
H
Kimura
T
T
Satoh
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D053607:Adrenomedullin; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004837:Epinephrine / Q000378:metabolism*; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D013153:Splanchnic Nerves / Q000502:physiology
D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; C104782:adrenomedullin (22-52); D053607:Adrenomedullin; D000109:Acetylcholine; D009638:Norepinephrine; D004837:Epinephrine