title: Pharmacological and genetic identification of serotonin receptor subtypes on Drosophila larval heart and aorta.
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.
authors.affiliation: Department of Biology and Center for Muscle Biology, University of Kentucky, 675 Rose Street, Lexington, KY, 40506-0225, USA, zana.majeed@uky.edu.
authors.forename: Zana R
authors.initials: ZR
authors.lastname: Majeed
authors.forename: Audra
authors.initials: A
authors.lastname: Stacy
authors.forename: Robin L
authors.initials: RL
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004330:Drosophila / Q000187:drug effects / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007650:Ketanserin / Q000494:pharmacology; D007814:Larva / Q000187:drug effects; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D034622:RNA Interference; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism; D044403:Receptor, Serotonin, 5-HT2B / Q000378:metabolism; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D029721:Drosophila Proteins; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C042390:alpha-methylserotonin; D012701:Serotonin; D007650:Ketanserin