title: P2 receptors modulate respiratory rhythm but do not contribute to central CO2 sensitivity in vitro.
abstract: Multiple brainstem sites are proposed to contribute to central respiratory chemosensitivity, however, the underlying molecular mechanisms remain unknown. P2X2 subunit-containing ATP receptors, which mediate pH-sensitive currents, appear to contribute to central chemosensitivity in vivo [J. Physiol. 523 (2000) 441]. However, recent data from P2X2 knockout mice [J. Neurosci. 23 (2003) 11315] indicate that they are not essential. To further explore the role of P2 receptors in central chemosensitivity, we examined the effects of P2 receptor agonists/antagonists on respiratory-related activity and CO2-sensitivity of rhythmically-active in vitro preparations from neonatal rat. Our main findings: (i) that putative chemosensitive regions of the ventrolateral medulla are immunoreactive for the P2X2 subunit; (ii) that ATP potentiates respiratory frequency in a dose-dependent, and PPADS-sensitive (P2 receptor antagonist), manner; and (iii) that the increase in burst frequency produced by increasing CO2 is unaffected by PPADS, indicate that ATP is a potent modulator of respiratory activity, but that P2 receptors do not contribute to central chemosensitivity in vitro.
authors.affiliation: Department of Physiology, Faculty of Medicine and Health Science, University of Auckland, Private Bag 92019, New Zealand.
authors.forename: A R
authors.initials: AR
authors.lastname: Lorier
authors.forename: K
authors.initials: K
authors.lastname: Peebles
authors.forename: T
authors.initials: T
authors.lastname: Brosenitsch
authors.forename: D M
authors.initials: DM
authors.lastname: Robinson
authors.forename: G D
authors.initials: GD
authors.lastname: Housley
authors.forename: G D
authors.initials: GD
authors.lastname: Funk
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002245:Carbon Dioxide / Q000378:metabolism* / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D012119:Respiration / Q000187:drug effects
chemical_list: D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D002245:Carbon Dioxide; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate