Central Action of Adrenomedullin to Inhibit Gastric Emptying in Rats

The central action of human adrenomedullin (AM) to influence gastric emptying and the peripheral mechanisms involved were studied in conscious rats. The 20-min rate of gastric emptying of a methylcellulose solution was assessed after intracisternal (ic) injection of AM or rat α-calcitonin gene-related peptide (αCGRP). AM and αCGRP dose-dependently inhibited gastric emptying with ic ED50 values of 120 and 100 pmol, respectively. Human proadrenomedullin N-terminal 20 peptide (150–600 pmol, ic) and AM (150 pmol, iv) had no effect. The inhibitory actions of AM and αCGRP (150 pmol, ic) were completely blocked by the CGRP antagonist, human CGRP-(8–37) injected ic at 30 μg, but not at 15 μg. The CRF antagonist,[ d-Phe12,Nle21,38,CαMeLeu37]CRF-(12–41) (10 μg/rat) injected ic prevented ic rat/human CRF (150 pmol)-induced 53% inhibition of gastric emptying while not modifying the effect of AM. The action of AM (150 pmol, ic) was abolished by bilateral adrenalectomy or the β-adrenergic blocker, propranolol (1 mg/kg,...