title: Nicotinic receptor activation occludes purinergic control of central cardiorespiratory network responses to hypoxia/hypercapnia.
abstract: Prenatal nicotine exposure alters the cardiorespiratory network responses to hypoxia/hypercapnia; however the mechanism(s) responsible for these cardiorespiratory network responses and their alteration by prenatal nicotine exposure are unknown. We used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and excitatory synaptic neurotransmission to cardioinhibitory vagal neurons (CVNs). Respiratory related increases in glutamatergic neurotransmission only occurred on recovery from hypoxia/hypercapnia in unexposed animals. These responses were not altered by nicotinic antagonists but were mediated in part by activation of P2 purinergic receptors. Prenatal nicotine exposure transformed central cardiorespiratory responses to hypoxia/hypercapnia; CVNs received a respiratory related glutamatergic neurotransmission during periods of hypoxia and hypercapnia, whereas increases in glutamatergic neurotransmission during recovery were absent. The excitatory neurotransmission to CVNs during hypoxia/hypercapnia in prenatal nicotine-exposed animals were wholly dependent on nicotinic receptor activation. In the presence of nicotinic antagonists, the responses in prenatal nicotine animals reverted to the pattern of responses in unexposed animals in which an increase in glutamatergic neurotransmission occurred not during but only on recovery from hypoxia/hypercapnia, and this recruited excitatory pathway was blocked by P2 receptor antagonists. These data identify a new functional role for purinergic receptors in the cardiorespiratory responses to hypoxia/hypercapnia and their role in occluding nicotinic receptor activation with prenatal nicotine exposure.
authors: Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037, USA.
authors: Z G
authors: ZG
authors: Huang
authors: K J S
authors: KJ
authors: Griffioen
authors: X
authors: X
authors: Wang
authors: O
authors: O
authors: Dergacheva
authors: H
authors: H
authors: Kamendi
authors: C
authors: C
authors: Gorini
authors: D
authors: D
authors: Mendelowitz
mesh_terms: D000818:Animals; D001049:Apnea / Q000503:physiopathology; D001933:Brain Stem / Q000502:physiology; D002319:Cardiovascular System / Q000294:innervation* / Q000503:physiopathology*; D003627:Data Interpretation, Statistical; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D058914:Purinergic Antagonists; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*; D011983:Receptors, Purinergic / Q000502:physiology*; D012137:Respiratory System / Q000294:innervation* / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology
chemical_list: D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D058914:Purinergic Antagonists; D011978:Receptors, Nicotinic; D011983:Receptors, Purinergic