Chemoreceptor activity is normal in mice lacking the NK1 receptor.
Substance P has been proposed to be an important neurotransmitter in the carotid body with the neurokinin 1 (NK1) receptor, mediating excitation between the glomus cells and afferent nerve endings. In order to better understand the role of substance P, this study examined chemoreceptor afferent activity, in vitro, and tissue catecholamine levels and release in adult, wild-type mice and mice lacking the gene for the NK1 receptor (NK1-KO). Groups did not differ significantly in body weight, carotid body dopamine content or carotid body norepinephrine content. In wild-type mice, single unit activity increased from 0.59 +/- 0.14 Hz to 19.78 +/- 2.27 Hz during superfusion with strong hypoxia (PO2 approximately 25 Torr). Chemoreceptor activity in NK1-KO mice, increased from 0.71 +/- 0.23 to 21.50 +/- 3.62 Hz, and neither baseline or peak frequencies were significantly different from the wild-type group. Less severe hypoxia (PO2 approximately 45 torr), evoked peak activities of 12.50 +/- 1.88 and 10.64 +/- 3.72 Hz in wild-type and NK1-KO mice, which were also not significantly different. In response to severe hypoxia, free-tissue catecholamine increased to 4.92 +/- 0.85 microm in wild-type mice and 4.26 +/- 0.63 microm in NK1-KO mice, which were also not significantly different. It may therefore be concluded that loss of NK1 receptors has little effect on chemoreceptor function in the mouse, and thus they play, at best, a minor role in the hypoxic chemoreception process.
Rigual
Ricardo
R
Departamento de Bioquímica y Biología Molecular y Fisiología/Instituto de Biología y Genética Molecular Facultad de Medicina, Universidad de Valladolid/Consejo Superior de Investigaciones Científicas, Valladolid, Spain. rrigual@ibgm.uva.es
Rico
Alberto J
AJ
Prieto-Lloret
Jesus
J
de Felipe
Carmen
C
González
Constancio
C
Donnelly
David F
DF
D000818:Animals; D002344:Carotid Body / Q000166:cytology / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000172:deficiency* / Q000235:genetics; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013373:Substance P / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D017833:Visceral Afferents / Q000166:cytology / Q000378:metabolism*
D002395:Catecholamines; D018040:Receptors, Neurokinin-1; D013373:Substance P; D004298:Dopamine; D009638:Norepinephrine