Pharmacological and genetic identification of serotonin receptor subtypes on Drosophila larval heart and aorta

Zana R. Majeed, Audra Stacy, Robin L. Cooper

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Serotonin, 5-hydroxytryptamine (5-HT), plays various roles in the fruit fly, Drosophila melanogaster. Previous studies have shown that 5-HT modulates the heart rate in third instar larvae. However, the receptor subtypes that mediate 5-HT action in larval cardiac tissue had yet to be determined. In this study, various 5-HT agonists and antagonists were employed to determine which 5-HT receptor subtypes are responsible for the positive chronotropic effect by 5-HT. The pharmacological results demonstrate that a 5-HT2B agonist significantly increases the heart rate; however, 5-HT1A, 5-HT1B, and 5-HT7 agonists do not have a significant effect on the heart rate. Furthermore, 5-HT2 antagonist, ketanserin, markedly reduces the positive chronotropic effect of 5-HT in a dose-response manner. Furthermore, we employed genetic approaches to confirm the pharmacological results. For this purpose, we used RNA interference line to knock down 5-HT2ADro and also used 5-HT2ADro and 5-HT2BDro insertional mutation lines. The results show that 5-HT2ADro or 5-HT2BDro receptor mutations reduce the response of the heart to 5-HT. Given these results, we conclude that these 5-HT2 receptor subtypes are involved in the action of 5-HT on the heart rate in the larval stage.

Original languageEnglish
Pages (from-to)205-219
Number of pages15
JournalJournal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology
Volume184
Issue number2
DOIs
StatePublished - Feb 2014

Bibliographical note

Funding Information:
Acknowledgments We thank Dr. Olivier Thibault, and Dr. Douglas Harrison, University of Kentucky for suggestions and comments. This work was funded by American Physiology Society Undergraduate Research Fellowship and G. Ribble fellowship from Dept. of Biology, Univ. of KY (AS), the Higher Committee for Education Development (HCED) scholarship in Iraq (ZRM) and personal funds (RLC).

Keywords

  • 5-HT
  • 5-HT receptors agonists and antagonists
  • 5-HT2ADro and 5-HT2BDro receptors mutations
  • Heart rate

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry
  • Physiology
  • Animal Science and Zoology
  • Endocrinology

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