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Department of Pharmacology, Temple University School of Medicine, 3420 N. Broad Street, Philadelphia, Pennsylvania 19140, USA
¹ Phoenix Pharmaceuticals Inc., Belmont, California 94002, USA

(Requests for offprints should be addressed to N J Dun; Email: ndun{at}temple.edu)

Obestatin, a 23 amino acid peptide recently isolated from the rat stomach, is encoded by the same gene that encodes ghrelin. With the use of an antiserum directed against the mouse/rat obestatin, obestatin immunoreactivity (irOBS) was detected in cells of the gastric mucosa, myenteric plexus, and in Leydig cells of the testis in Sprague–Dawley rats. Double labeling the myenteric plexus with obestatin antiserum and choline acetyltransferase (ChAT) antiserum revealed that nearly all irOBS neurons were ChAT positive and vice versa. For comparative purposes, myenteric ganglion cells, cells in the gastric mucosa, and Leydig cells of the testis were shown to be immunoreactive to preproghrelin. The biological activity of obestatin on rat central neurons was assessed by the calcium microfluorimetric Fura-2 method. Obestatin (100 nM) administered to dissociated and cultured rat cerebral cortical neurons elevated cytosolic calcium concentrations [Ca²⁺]_i in a population of cortical neurons. The result provides the first immunohistochemical evidence that obestatin is expressed in cells of the gastric mucosa and myenteric ganglion cells, and also in Leydig cells of the testis; the peptide is biologically active on central neurons.

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				J. V. Zhang, H. Jahr, C.-W. Luo, C. Klein, K. Van Kolen, L. Ver Donck, A. De, E. Baart, J. Li, D. Moechars, et al. Obestatin Induction of Early-Response Gene Expression in Gastrointestinal and Adipose Tissues and the Mediatory Role of G Protein-Coupled Receptor, GPR39 Mol. Endocrinol., June 1, 2008; 22(6): 1464 - 1475. [Abstract] [Full Text] [PDF]

				W. K Samson, G. L C Yosten, J.-K. Chang, A. V Ferguson, and M. M White Obestatin inhibits vasopressin secretion: evidence for a physiological action in the control of fluid homeostasis J. Endocrinol., March 1, 2008; 196(3): 559 - 564. [Abstract] [Full Text] [PDF]

				J. V. Zhang, C. Klein, P.-G. Ren, S. Kass, L. V. Donck, D. Moechars, and A. J. W. Hsueh Response to Comment on "Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake" Science, February 9, 2007; 315(5813): 766d - 766d. [Abstract] [Full Text] [PDF]