AREGU Apr. 45/4

Masada, Kimiya, Takahiro Nagayama, Akio Hosokawa, Makoto Yoshida, Mizue Suzuki-Kusaba, Hiroaki Hisa, Tomohiko Kimura, and Susumu Satoh. Effects of adrenomedullin and PAMP on adrenal catecholamine release in dogs. Am. J. Physiol. 276 (Regulatory Integrative Comp. Physiol. 45): R1118–R1124, 1999.—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 μg) produced frequencyor dose-dependent increases in adrenal catecholamine output. These responses were unaffected by infusion of adrenomedullin (1, 3, and 10 ng·kg21 ·min21) or its selective antagonist adrenomedullin-(22—52) (5, 15, and 50 ng · kg21 ·min21). Proadrenomedullin NH2-terminal 20 peptide (PAMP; 5, 15, and 50 ng·kg21 ·min21) suppressed both the splanchnic nerve stimulationand 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 μg) and to muscarine (0.5, 1, and 2 μg), 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.