HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 34, 32058-32067, August 22, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/34/32058    most recent M305545200v1 Submit a Letter to Editor 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 Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mahata, S. K. Articles by O'Connor, D. T. Search for Related Content PubMed PubMed Citation Articles by Mahata, S. K. Articles by O'Connor, D. T. Social Bookmarking                      What's this?

Catecholamine Secretory Vesicle Stimulus-Transcription Coupling in Vivo

DEMONSTRATION BY A NOVEL TRANSGENIC PROMOTER/PHOTOPROTEIN REPORTER AND INHIBITION OF SECRETION AND TRANSCRIPTION BY THE CHROMOGRANIN A FRAGMENT CATESTATIN^*

Sushil K. Mahata, Nitish R. Mahapatra, Manjula Mahata, Timothy C. Wang, Brian P. Kennedy, Michael G. Ziegler and Daniel T. O'Connor 

From the Department of Medicine and Center for Molecular Genetics, University of California, and Veterans Affairs San Diego Healthcare System, San Diego, California 92161, and the Department of Medicine, University of Massachusetts, Worcester, Massachusetts 01655

Stimulation of chromaffin cell secretion in vitro triggers not only secretion but also resynthesis of just released catecholamines and chromogranin A, the precursor of the catecholamine release-inhibitory, nicotinic cholinergic antagonist peptide catestatin. Does stimulus-transcription coupling occur in vivo? And does catestatin antagonize secretion and transcription in vivo? To answer these questions, we employed a novel mouse strain harboring a chromogranin A promoter/firefly luciferase reporter transgene. Tissue-specific expression of the reporter was established by both luminescence and reverse transcription-PCR. Secretion and transcription in vivo were triggered by either direct nicotinic stimulation or vesicular transmitter depletion. Nicotinic blockade in vivo was attempted with either the classical antagonist chlorisondamine or the novel antagonist catestatin. Luciferase reporter expression was exquisitely sensitive over a large dynamic range, was specific for the transgenic animals, and paralleled typical neuroendocrine distribution of endogenous chromogranin A. Adrenal ontogeny revealed a rise of embryonic transgene expression until embryonal day 18, with an abrupt postnatal decline. Direct nicotinic stimulation of chromaffin cells caused catecholamine release and transgene transcription, each of which was nearly completely blocked by chlorisondamine. Similar adrenal results were obtained during vesicular catecholamine depletion. Both secretion and transcription were substantially blocked in the adrenal gland by catestatin. In brain and sympathetic nerve, stimulation of transcription was more modest, and reserpine responses were only incompletely blocked by chlorisondamine or catestatin, perhaps because of limited blood-brain barrier penetration by these cationic antagonists. Thus, nicotinic cholinergic stimulus-transcription coupling occurs in vivo and can be provoked either directly or indirectly (by vesicular transmitter depletion). Such coupling triggers the biosynthesis of chromogranin A, the precursor of catestatin. Catestatin itself blocks stimulation of both secretion and transcription in vivo. Thus, chromogranin A and its catestatin fragment may lie at the nexus of nicotinic cholinergic signaling in vivo.

Received for publication, May 27, 2003 , and in revised form, June 5, 2003.

^* This work was supported by National Institutes of Health grants (to D. T. O. C. and S. K. M.) and by the Department of Veterans Affairs (to D. T. O. C. and S. K. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Medicine and Center for Molecular Genetics, University of California at San Diego, and VASDHS (9111H), 3350 La Jolla Village Dr., San Diego, CA 92161. Tel.: 858-552-8585 (ext. 7373); Fax: 858-642-6331; E-mail: doconnor{at}ucsd.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. R. Mahapatra Catestatin is a novel endogenous peptide that regulates cardiac function and blood pressure Cardiovasc Res, December 1, 2008; 80(3): 330 - 338. [Abstract] [Full Text] [PDF]

				T. Angelone, A. M. Quintieri, B. K. Brar, P. T. Limchaiyawat, B. Tota, S. K. Mahata, and M. C. Cerra The Antihypertensive Chromogranin A Peptide Catestatin Acts as a Novel Endocrine/Paracrine Modulator of Cardiac Inotropism and Lusitropism Endocrinology, October 1, 2008; 149(10): 4780 - 4793. [Abstract] [Full Text] [PDF]

				R. Mazza, A. Gattuso, C. Mannarino, B. K. Brar, S. F. Barbieri, B. Tota, and S. K. Mahata Catestatin (chromogranin A344-364) is a novel cardiosuppressive agent: inhibition of isoproterenol and endothelin signaling in the frog heart Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H113 - H122. [Abstract] [Full Text] [PDF]

				F. Rao, G. Wen, J. R. Gayen, M. Das, S. M. Vaingankar, B. K. Rana, M. Mahata, B. P. Kennedy, R. M. Salem, M. Stridsberg, et al. Catecholamine Release-Inhibitory Peptide Catestatin (Chromogranin A352-372): Naturally Occurring Amino Acid Variant Gly364Ser Causes Profound Changes in Human Autonomic Activity and Alters Risk for Hypertension Circulation, May 1, 2007; 115(17): 2271 - 2281. [Abstract] [Full Text] [PDF]

				T. Moriguchi, N. Takako, M. Hamada, A. Maeda, Y. Fujioka, T. Kuroha, R. E. Huber, S. L. Hasegawa, A. Rao, M. Yamamoto, et al. Gata3 participates in a complex transcriptional feedback network to regulate sympathoadrenal differentiation Development, October 1, 2006; 133(19): 3871 - 3881. [Abstract] [Full Text] [PDF]

				T. Kim, M. C. Gondre-Lewis, I. Arnaoutova, and Y. P. Loh Dense-Core Secretory Granule Biogenesis Physiology, April 1, 2006; 21(2): 124 - 133. [Abstract] [Full Text] [PDF]

				D. T. O'Connor, P. E. Cadman, C. Smiley, R. M. Salem, F. Rao, J. Smith, S. D. Funk, S. K. Mahata, M. Mahata, G. Wen, et al. Pancreastatin: Multiple Actions on Human Intermediary Metabolism in Vivo, Variation in Disease, and Naturally Occurring Functional Genetic Polymorphism J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5414 - 5425. [Abstract] [Full Text] [PDF]

				S. K. Mahata, M. Mahata, G. Wen, W. B. Wong, N. R. Mahapatra, B. A. Hamilton, and D. T. O'Connor The Catecholamine Release-Inhibitory "Catestatin" Fragment of Chromogranin A: Naturally Occurring Human Variants with Different Potencies for Multiple Chromaffin Cell Nicotinic Cholinergic Responses Mol. Pharmacol., November 1, 2004; 66(5): 1180 - 1191. [Abstract] [Full Text] [PDF]