L-type calcium channels contribute to 5-HT3-receptor-evoked CaMKIIα and ERK activation and induction of emesis in the least shrew (Cryptotis parva)

European Journal of Pharmacology
Tarun E HutchinsonNissar A Darmani

Abstract

Activation of serotonergic 5-HT3 receptors by its selective agonist 2-methyl serotonin (2-Me-5-HT) induces vomiting, which is sensitive to selective antagonists of both 5-HT3 receptors (palonosetron) and L-type calcium channels (LTCC) (amlodipine or nifedipine). Previously we demonstrated that 5-HT3 receptor activation also causes increases in a palonosetron-sensitive manner in: i) intracellular Ca(2+) concentration, ii) attachment of calmodulin (CaM) to 5-HT3 receptor, and iii) phosphorylation of Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) and extracellular-signal-regulated kinase 1/2 (ERK1/2). Here, we investigate the role of the short-acting LTCC blocker nifedipine on 2-Me-5-HT-evoked intracellular Ca(2+) increase and on downstream intracellular emetic signaling, which have been shown to be coupled with 2-Me-5-HT׳s emetic effects in the least shrew. Using the cell-permeant Ca(2+) indicator fluo-4 AM, here we present evidence for the contribution of Ca(2+) influx through LTCCs (sensitive to nifedipine) in 2-Me-5-HT (1µM) -evoked rise in cytosolic Ca(2+) levels in least shrew brainstem slices. Nifedipine pretreatment (10mg/kg, s.c.) also suppressed 2-Me-5-HT-evoked interaction of 5-HT3 receptors with CaM as well a...Continue Reading

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Mar 19, 2014·Pharmacology, Biochemistry, and Behavior·Weixia ZhongNissar A Darmani

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Citations

Nov 7, 2015·Nature Reviews. Drug Discovery·Gerald W Zamponi
May 12, 2017·British Journal of Pharmacology·Vincent MartinLaurence Lanfumey
Jun 9, 2017·Journal of Translational Medicine·Isabella VillaIleana Terruzzi
Apr 18, 2021·Autonomic Neuroscience : Basic & Clinical·Louiza BelkacemiNissar A Darmani
Jun 3, 2021·International Journal of Molecular Sciences·Weixia ZhongNissar A Darmani

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