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Urocortin-1 Infusion in Normal Humans

Christchurch Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, University of Otago (M.E.D., C.J.P., T.G.Y., J.G.L., M.T.R., C.M.F., A.M.R.), Christchurch 8001, New Zealand; and Department of Medicine, University of the United Arab Emirates (M.G.N.), Al Ain, United Arab Emirates

Address all correspondence and requests for reprints to: Dr. Mark E. Davis, Research Fellow, Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand. E-mail: mark.davis{at}chmeds.ac.nz.

Urocortin-1 (Ucn-1), a member of the corticotropin-releasing factor family, has been shown in animal studies to have effects on the pituitary-adrenal axis, the cardiovascular system, circulating neurohormones, and renal function and to suppress appetite. For the first time in man we have evaluated these effects of infused Ucn-1 as well as actions on plasma ghrelin, a hormone known to increase appetite. We also assessed Ucn-1 pharmacokinetics. Eight healthy male volunteers consuming a diet of constant sodium and potassium content received 50 µg Ucn-1 iv over 1 h in a placebo-controlled, randomized, time-matched, cross-over study. Ucn-1 infusion compared with placebo increased plasma levels of corticotropin [44.6 ± 7.7 vs. 19.1 ± 3.2 pg/ml (9.5 ± 1.7 vs. 4.2 ± 0.7 pmol/liter); P < 0.001], cortisol [15.6 ± 1.6 vs. 7.7 ± 1.4 µg/dl (432 ± 43 vs. 213 ± 40 nmol/liter); P < 0.001], and atrial natriuretic peptide [26.2 ± 3.4 vs. 21.3 ± 2.2 pg/ml [8.5 ± 1.1 vs. 6.9 ± 0.7 pmol/liter); P = 0.019] while suppressing plasma ghrelin (P = 0.008). No hemodynamic or renal effects were observed at the dose used. The plasma Ucn-1 t_1/2 was 52 min based on a one-compartment model. In conclusion, a brief iv infusion of 50 µg Ucn-1 stimulates plasma ACTH, cortisol, and atrial natriuretic peptide secretion and suppresses plasma ghrelin in healthy male volunteers. The latter effect might contribute to the anorexic action of Ucn-1.

This work was supported by the National Heart Foundation and Health Research Council of New Zealand.

Abbreviations: ADM, Adrenomedullin; ANP, atrial natriuretic peptide; AVP, arginine vasopressin; BNP, brain natriuretic peptide; CRF, corticotropin-releasing factor; CRF-BP, corticotropin-releasing factor-binding protein; CRF-RI, corticotropin-releasing factor receptor type 1; CV, coefficient of variation; ET, endothelin; PRA, plasma renin activity; PRL, prolactin.

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