This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Davis, M. E. Articles by Richards, A. M. Search for Related Content PubMed PubMed Citation Articles by Davis, M. E. Articles by Richards, A. M.

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.

This article has been cited by other articles:

				M. E. Davis, C. J. Pemberton, T. G. Yandle, S. F. Fisher, J. G. Lainchbury, C. M. Frampton, M. T. Rademaker, and M. Richards Urocortin 2 infusion in human heart failure Eur. Heart J., November 1, 2007; 28(21): 2589 - 2597. [Abstract] [Full Text] [PDF]

				W.H. W. Tang and G. S. Francis Exploring new drugs for heart failure: the case of urocortin Eur. Heart J., November 1, 2007; 28(21): 2561 - 2562. [Full Text] [PDF]

				B. G. Helwig, T. I. Musch, R. A. Craig, and M. J. Kenney Increased interleukin-6 receptor expression in the paraventricular nucleus of rats with heart failure Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1165 - R1173. [Abstract] [Full Text] [PDF]

				M. E. Davis, C. J. Pemberton, T. G. Yandle, S. F. Fisher, J. G. Lainchbury, C. M. Frampton, M. T. Rademaker, and A. M. Richards Urocortin 2 Infusion in Healthy Humans: Hemodynamic, Neurohormonal, and Renal Responses J. Am. Coll. Cardiol., January 30, 2007; 49(4): 461 - 471. [Abstract] [Full Text] [PDF]

				L. Wang, N. R. Basa, A. Shaikh, A. Luckey, D. Heber, D. H. St-Pierre, and Y. Tache LPS inhibits fasted plasma ghrelin levels in rats: role of IL-1 and PGs and functional implications. Am J Physiol Gastrointest Liver Physiol, October 1, 2006; 291(4): G611 - G620. [Abstract] [Full Text] [PDF]

				M. T. Rademaker, V. A. Cameron, C. J. Charles, and A. M. Richards Integrated Hemodynamic, Hormonal, and Renal Actions of Urocortin 2 in Normal and Paced Sheep: Beneficial Effects in Heart Failure Circulation, December 6, 2005; 112(23): 3624 - 3632. [Abstract] [Full Text] [PDF]

				M. T. Rademaker, C. J. Charles, E. A. Espiner, C. M. Frampton, J. G. Lainchbury, and A. M. Richards Four-day urocortin-I administration has sustained beneficial haemodynamic, hormonal, and renal effects in experimental heart failure Eur. Heart J., October 1, 2005; 26(19): 2055 - 2062. [Abstract] [Full Text] [PDF]

				M. Kojima and K. Kangawa Ghrelin: Structure and Function Physiol Rev, April 1, 2005; 85(2): 495 - 522. [Abstract] [Full Text] [PDF]