Hypoxia transduction by carotid body chemoreceptors in mice lacking dopamine D(2) receptors.
Hypoxia-induced dopamine (DA) release from carotid body (CB) glomus cells and activation of postsynaptic D(2) receptors have been proposed to play an important role in the neurotransmission process between the glomus cells and afferent nerve endings. To better resolve the role of D(2) receptors, we examined afferent nerve activity, catecholamine content and release, and ventilation of genetically engineered mice lacking D(2) receptors (D(2)(-/-) mice). Single-unit afferent nerve activities of D(2)(-/-) mice in vitro were significantly reduced by 45% and 25% compared with wild-type (WT) mice during superfusion with saline equilibrated with mild hypoxia (Po(2) approximately 50 Torr) or severe hypoxia (Po(2) approximately 20 Torr), respectively. Catecholamine release in D(2)(-/-) mice was enhanced by 125% in mild hypoxia and 75% in severe hypoxia compared with WT mice, and the rate of rise was increased in D(2)(-/-) mice. We conclude that CB transduction of hypoxia is still present in D(2)(-/-) mice, but the response magnitude is reduced. However, the ventilatory response to acute hypoxia is maintained, perhaps because of an enhanced processing of chemoreceptor input by brain stem respiratory nuclei.
Departamento de Bioquímica y Biología Molecular y Fisiología/Instituto de Biología y Genética Molecular (IBGM) Universidad de Valladolid/Consejo Superior de Investigaciones Científicas (CSIC) Facultad de Medicina, C/Ramón y Cajal, 47005 Valladolid, Spain.
J
J
Prieto-Lloret
D F
DF
Donnelly
A J
AJ
Rico
R
R
Moratalla
C
C
González
R J
RJ
Rigual
D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D002344:Carotid Body / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D012123:Pulmonary Ventilation / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D017448:Receptors, Dopamine D2; D004298:Dopamine; D009638:Norepinephrine