ArticleJournal of applied physiology (Bethesda, Md. : 1985)2013
5-HT stimulation of heart rate in Drosophila does not act through cAMP as revealed by pharmacogenetics.
Article in Journal of applied physiology (Bethesda, Md. : 1985), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
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- Activation of cyclic AMP signaling pathway in dopaminergic neurons rescues locomotion defects in a Drosophila larval model of Parkinson's disease.Brain research · 2024Article
- Effect of Temperature on Heart Rate forInsects · 2021Article
- The effects of tricaine mesylate on arthropods: crayfish, crab and Drosophila.Invertebrate neuroscience : IN · 2020Article
- Effects of inhibiting mTOR with rapamycin on behavior, development, neuromuscular physiology and cardiac function in larvalBiology open · 2019Article
- The Effects of Chloride Flux onMethods and protocols · 2019Article
- Modulatory effects on Drosophila larva hearts: room temperature, acute and chronic cold stress.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2016Article
- Pharmacological identification of cholinergic receptor subtypes on Drosophila melanogaster larval heart.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2016Article
- Model Organisms in G Protein-Coupled Receptor Research.Molecular pharmacology · 2015Review
- Pharmacological and genetic identification of serotonin receptor subtypes on Drosophila larval heart and aorta.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2014Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The fruit fly, Drosophila melanogaster, is a good experimental organism to study the underlying mechanism of heart rate (HR) regulation. It is already known that many neuromodulators (serotonin, dopamine, octopamine, acetylcholine) change the HR in Drosophila melanogaster larvae. In this study, we investigated the role of cAMP-PKA signaling pathway in HR regulation and 5-HT positive chronotropic action. In order to obtain insight into the 5-HT mechanism of action in larvae cardiomyocytes, genetic and pharmacological approaches were used. We used transgenic flies that expressed the hM4Di receptor [designer receptors exclusively activated by designer drugs (DREADDs)] as one tool. Our previous results showed that activation of hM4Di receptors (modified muscarinic acetylcholine receptors) decreases or arrests the heart from beating. In this study, it was hypothesized that the positive chronotropic effect of serotonin [5-hydroxytryptamine (5-HT)] are mediated by serotonin receptors coupled to the adenylyl cyclase pathway and downstream cAMP and PKA activity. Activation of hM4Di by clozapine-N-oxide (CNO) was predicted to block the effects of serotonin by inhibiting adenylyl cyclase activity through Gαi pathway activation. Interestingly, we found here that manipulation of adenylyl cyclase activity and cAMP levels had no significant effect on HR. The ability of hM4Di receptor activation to slow or stop the heart is therefore likely mediated by activation of GIRK channels to produce hyperpolarization of cardiomyocytes, and not through inhibition of adenylyl cyclase.
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