QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Willoughby, D. Articles by Benjamin, P. R. Search for Related Content PubMed PubMed Citation Articles by Willoughby, D. Articles by Benjamin, P. R. Social Bookmarking                         What's this?

Journal of Experimental Biology, Vol 202, Issue 19 2581-2593, Copyright © 1999 by Company of Biologists

JOURNAL ARTICLES

Inositol-1,4,5-trisphosphate and inositol-1,3,4,5-tetrakisphosphate are second messenger targets for cardioactive neuropeptides encoded on the FMRFamide gene

D Willoughby, MS Yeoman and PR Benjamin
Sussex Centre for Neuroscience, School of Biological Sciences, University of Sussex, Brighton BN1 9QG, UK. dw212@cam.ac.uk.

This paper examines the importance of the calcium-mobilizing inositol phosphate pathway in mediating the effects of FMRFamide and its gene-related neuropeptides on the myogenic heart beat of the pond snail Lymnaea stagnalis. These peptides are encoded on a single exon of the FMRFamide gene and mediate diverse physiological effects in the isolated heart. The rate of production of inositol-1,4, 5-trisphosphate [Ins(1,4,5)P(3)] and inositol-1,3,4, 5-tetrakisphosphate [Ins(1,3,4,5)P(4)], measured using an HPLC method, were both significantly elevated in a concentration-dependent manner by FMRFamide (and were also elevated by FLRFamide). The threshold for increasing inositol phosphate production was low (100 pmol l(-1)) with a peak response occurring at 1 micromol l(-1) FMRFamide. The shape of the dose-response curve for FMRFamide-induced elevation of heart-beat frequency, obtained in pharmacological experiments on the isolated whole heart, was similar to that for stimulation of inositol phosphate levels in homogenized heart tissue. FMRFamide and Ins(1,4,5)P(3) produced similar effects on the rate of heart beat in permeabilized whole hearts. In addition, the phospholipase C inhibitor, neomycin (2.5 mmol l(-)(1)), blocked the stimulatory effects of FMRFamide on Ins(1, 4,5)P(3) production in heart homogenate, and attenuated the excitatory effects of this neuropeptide in the isolated heart. The 'isoleucine' pentapeptides, EFLRIamide and pQFYRIamide, also encoded by the FMRFamide gene, produced no significant effects on inositol phosphate production when applied alone or in combination with FMRFamide. These results suggested that FMRFamide (and FLRFamide), but not EFLRIamide and pQFYRIamide, mediated their main effects on heart beat via the inositol phosphate pathway. The fifth peptide, SEQPDVDDYLRDVVLQSEEPLY ('SEEPLY') had no effect when applied alone but appeared to modulate the effects of FMRFamide by delaying the time-to-peak of the Ins(1,4,5)P(3) response from 5 s to 20 s by an unknown mechanism.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. J. Perry, V. A. Straub, M. G. Schofield, J. F. Burke, and P. R. Benjamin Neuronal Expression of an FMRFamide-Gated Na+ Channel and Its Modulation by Acid pH J. Neurosci., August 1, 2001; 21(15): 5559 - 5567. [Abstract] [Full Text] [PDF]

				D Willoughby, M. Yeoman, and P. Benjamin Cyclic AMP is involved in cardioregulation by multiple neuropeptides encoded on the FMRFamide gene J. Exp. Biol., January 10, 1999; 202(19): 2595 - 2607. [Abstract] [PDF]