5-HT(2) receptor subtypes mediate different long-term changes in GABAergic activity to parasympathetic cardiac vagal neurons in the nucleus ambiguus.
Serotonin (5-HT), and in particular 5-HT(2) receptors, play an important role in cardiorespiratory function within the brainstem. In addition, abnormalities in the 5-HT system have been implicated in many cardiorespiratory disorders, including sudden infant death syndrome. However, little is known about the mechanisms of action of 5-HT(2) receptors in altering the activity of parasympathetic cardiac neurons in the brainstem. In this study we examined the effects of activation of different subtypes of 5-HT(2) receptors on spontaneous and respiratory-evoked GABAergic neurotransmission to cardioinhibitory vagal neurons within the nucleus ambiguus as well as rhythmic fictive inspiratory-related activity in rats. A single application of alpha-Me-5-hydroxytryptamine maleate (alpha-Me-5-HT), a 5-HT(2) receptor agonist, did not significantly alter the frequency of spontaneous or respiratory-evoked GABAergic inhibitory postsynaptic currents (IPSCs) in cardiac vagal neurons. However, repetitive successive applications of alpha-Me-5-HT elicited a long-lasting (>/=1 h) decrease in the frequency of spontaneous as well as inspiratory-related GABAergic IPSCs to cardiac vagal neurons. This study demonstrates multiple, but not single applications of the 5-HT(2) receptor agonist alpha-Me-5-HT caused a long-lasting inhibition of both spontaneous and fictive inspiratory-related GABAergic neurotransmission to CVNs, which can be prevented by the 5-HT(2B) receptor antagonist SB204741, but persisted with the 5-HT(2A/2C) receptor antagonist ketanserin. The 5-HT(2) receptor agonist alpha-Me-5-HT also reversibly and transiently excited central fictive inspiratory activity, which was abolished by ketanserin, but was unaffected by the 5-HT(2B) receptor antagonist SB204741.
Dergacheva
O
O
Department of Pharmacology and Physiology, George Washington University, Washington, DC 20037, USA.
Griffioen
K J S
KJ
Wang
X
X
Kamendi
H
H
Gorini
C
C
Mendelowitz
D
D
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006321:Heart / Q000294:innervation* / Q000502:physiology*; D007002:Hypoglossal Nerve / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D007211:Indoles; C092756:N-(1-methyl-5-indolyl)-N'-(3-methyl-5-isothiazolyl)urea; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C042390:alpha-methylserotonin; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D014508:Urea; D007650:Ketanserin