5HT2 Receptor Activation Facilitates P2X Receptor Mediated Excitatory Neurotransmission to Cardiac Vagal Neurons in the Nucleus Ambiguus
| Autor: | Olga Dergacheva, Qi Cheng, Harriet Kamendi, David Mendelowitz, Xin Wang, Christopher Gorini, Heather Jameson, Ramon Manchon Pinol |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Serotonin
Indoles medicine.drug_class Pyridines Action Potentials Thiophenes Neurotransmission P2 receptor In Vitro Techniques Article Nucleus Accumbens Rats Sprague-Dawley Cellular and Molecular Neuroscience Glutamatergic chemistry.chemical_compound medicine Animals PPADS Drug Interactions 5-HT receptor Pharmacology Neurons Chemistry Receptors Purinergic P2 5-HT2 receptor Purinergic receptor Excitatory Postsynaptic Potentials Vagus Nerve Receptor antagonist Rats Serotonin Receptor Agonists Animals Newborn Receptors Purinergic P2X Serotonin Antagonists Receptors Serotonin 5-HT2 Neuroscience Excitatory Amino Acid Antagonists |
| Popis: | Parasympathetic preganglionic cardiac vagal neurons (CVNs) which dominate the control of heart rate are located within the nucleus ambiguus (NA). Serotonin (5HT), and in particular 5HT2 receptors, play an important role in cardiovascular function in the brainstem. However, there is a lack of information on the mechanisms of action of 5HT2 receptors in modulating parasympathetic cardiac activity. This study tests whether activation of 5HT2 receptors alters excitatory glutamatergic and purinergic neurotransmission to CVNs. Application of alpha-methyl-5-hydroxytryptamine (alpha-Me-5HT), a 5HT2 agonist, reversibly increased both the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) in CVNs. Similar responses were obtained with alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine hydrochloride (BW723C86), and m-chlorophenylpiperazine (m-CPP), 5HT2B and 5HT2B/C receptor agonists, respectively. The facilitation evoked by alpha-Me-5HT was prevented by the 5HT2B/C receptor antagonist SB206553 hydrochloride (SB206553). Interestingly, the blockage of both NMDA and non-NMDA glutamatergic receptors did not prevent alpha-Me-5HT-evoked facilitation of mEPSCs, however, the responses were blocked by the P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). The responses evoked by alpha-Me-5HT were mimicked by application of alpha,beta-methylene ATP (alpha,beta-Me-ATP), a P2X receptor agonist, which were also blocked by PPADS. In summary, these results indicate activation of 5HT2 receptors facilitates excitatory purinergic, but not glutamatergic, neurotransmission to CVNs. |
| Databáze: | OpenAIRE |
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