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

J. Biol. Chem., Vol. 279, Issue 36, 37291-37297, September 3, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/36/37291    most recent M403819200v1 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 Bhattacharya, A. Articles by Singh, S. Search for Related Content PubMed PubMed Citation Articles by Bhattacharya, A. Articles by Singh, S. Social Bookmarking                      What's this?

Modulation of L-type Calcium Channels in Drosophila via a Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP)-mediated Pathway^*

Anindya Bhattacharya, Sukhwinder S. Lakhman, and Satpal Singh¶

From the Department of Pharmacology and Toxicology, State University of New York at Buffalo, Buffalo, New York 14214-3000

Modulation of calcium channels plays an important role in many cellular processes. Previous studies have shown that the L-type Ca²⁺ channels in Drosophila larval muscles are modulated via a cAMP-protein kinase A (PKA)-mediated pathway. This raises questions on the identity of the steps prior to cAMP, particularly the endogenous signal that may initiate this modulatory cascade. We now present data suggesting the possible role of a neuropeptide, pituitary adenylyl cyclase-activating polypeptide (PACAP), in this modulation. Mutations in the amnesiac (amn) gene, which encodes a polypeptide homologous to human PACAP-38, reduced the L-type current in larval muscles. Conditional expression of a wild-type copy of the amn gene rescued the current from this reduction. Bath application of human PACAP-38 also rescued the current. PACAP-38 did not rescue the mutant current in the presence of PACAP-6–38, an antagonist at type-I PACAP receptor. 2',5'-dideoxyadenosine, an inhibitor of adenylyl cyclase, prevented PACAP-38 from rescuing the amn current. In addition, 2',5'-dideoxyadenosine reduced the wild-type current to the level seen in amn, whereas it failed to further reduce the current observed in amn muscles. H-89, an inhibitor of PKA, suppressed the effect of PACAP-38 on the current. The above data suggest that PACAP, the type-I PACAP receptors, and adenylyl cyclase play a role in the modulation of L-type Ca²⁺ channels via cAMP-PKA pathway. The data also provide support for functional homology between human PACAP-38 and the amn gene product in Drosophila.

Received for publication, April 6, 2004 , and in revised form, June 15, 2004.

^* This work was supported by National Institutes of Health Grant GM-50779 and National Science Foundation Grant MCB-0094477. 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.

Present address: Roche Pharmaceuticals, 3431 Hillview Ave., R2-101, Palo Alto, CA 94304.

Present address: Dept. of Pharmaceutical Sciences, 527 Cooke Hall, State University of New York at Buffalo, NY 14260-1200.

^¶ To whom correspondence should be addressed: Dept. of Pharmacology and Toxicology, 102 Farber Hall, State University of New York at Buffalo, Buffalo, NY 14214-3000. Tel.: 716-829-2453; Fax: 716-829-2801; E-mail: singhs{at}buffalo.edu.

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

This article has been cited by other articles:

				W. Liu, R. Gnanasambandam, J. Benjamin, G. Kaur, P. B. Getman, A. J. Siegel, R. D. Shortridge, and S. Singh Mutations in Cytochrome c Oxidase Subunit VIa Cause Neurodegeneration and Motor Dysfunction in Drosophila Genetics, June 1, 2007; 176(2): 937 - 946. [Abstract] [Full Text] [PDF]

				J. D. Tompkins, J. C. Hardwick, S. A. Locknar, L. A. Merriam, and R. L. Parsons Ca2+ Influx, But Not Ca2+ Release From Internal Stores, Is Required for the PACAP-Induced Increase in Excitability in Guinea Pig Intracardiac Neurons J Neurophysiol, April 1, 2006; 95(4): 2134 - 2142. [Abstract] [Full Text] [PDF]

				Y. Matsumoto, S. Unoki, H. Aonuma, and M. Mizunami Critical role of nitric oxide-cGMP cascade in the formation of cAMP-dependent long-term memory Learn. Mem., January 1, 2006; 13(1): 35 - 44. [Abstract] [Full Text] [PDF]

				I. Harfi, F. Corazza, S. D'Hondt, and E. Sariban Differential Calcium Regulation of Proinflammatory Activities in Human Neutrophils Exposed to the Neuropeptide Pituitary Adenylate Cyclase-Activating Protein J. Immunol., September 15, 2005; 175(6): 4091 - 4102. [Abstract] [Full Text] [PDF]