Effects of adrenomedullin and PAMP on adrenal catecholamine release in dogs

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 1999-04, Vol.276 (4), p.R1118
• Main Authors: Masada, Kimiya, Nagayama, Takahiro, Hosokawa, Akio, Yoshida, Makoto, Suzuki-Kusaba, Mizue, Hisa, Hiroaki, Kimura, Tomohiko, Satoh, Susumu
• Format: Article
• Language: English
• ISSN: 1522-1490
• DOI: 10.1152/ajpregu.1999.276.4.R1118

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 frequency- or dose-dependent increases in adrenal catecholamine output. These responses were unaffected by infusion of adrenomedullin (1, 3, and 10 ng ⋅ kg ⋅ min ) or its selective antagonist adrenomedullin-(22-52) (5, 15, and 50 ng ⋅ kg ⋅ min ). Proadrenomedullin NH -terminal 20 peptide (PAMP; 5, 15, and 50 ng ⋅ kg ⋅ min ) 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 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.