Stimulus-specific signaling pathways in rabbit carotid body chemoreceptors.
The carotid body is an arterial chemosensory organ which responds to multiple natural and pharmacological stimuli, including hypoxia and nicotine. Numerous studies have investigated the initial molecular events which activate chemosensory type I cells in the carotid body, but less attention has been focused on later steps in the transduction cascade, which mediate neurotransmitter release from type I cells and excitation of chemoreceptor afferent fibers in the carotid sinus nerve. In the present study, we examined the effects of a highly specific inhibitor of calcium/calmodulin-dependent kinase II, KN-62, and a calmodulin inhibitor, trifluoperazine, on carotid sinus nerve activity and catecholamine release evoked from rabbit carotid bodies superfused in vitro. KN-62 did not alter sinus nerve activity and catecholamine release evoked by hypoxia, but this agent significantly reduced nerve activity and neurotransmitter release evoked by 100 microM nicotine. Trifluoperazine (10 microM), likewise inhibited activity evoked by nicotine, as well as hypoxia. Basal levels of nerve activity and catecholamine release (established in superfusate equilibrated with 100% O2) were unaffected by all drug treatments. Separate biochemical experiments showed that Ca2+/calmodulin-dependent incorporation of 32P into carotid body particulate proteins is significantly reduced following incubation of intact carotid bodies in nicotine, but not following exposure to hypoxia. Our observations suggest that excitation of the carotid body by diverse stimuli may involve the activation of distinct, stimulus-specific transduction pathways. Furthermore, these data correlate with our previous findings which showed that hypoxia, on the one hand, and nicotine on the other, evoke the preferential release of either dopamine or norepinephrine, respectively, from carotid bodies incubated in vitro.
Chen
J
J
Department of Physiology, University of Utah School of Medicine, Salt Lake City 84108, USA.
He
L
L
Dinger
B
B
Fidone
S
S
D000818:Animals; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D002344:Carotid Body / Q000502:physiology*; D002346:Carotid Sinus / Q000294:innervation; D002395:Catecholamines / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000502:physiology*; D009424:Nervous System Physiological Phenomena; D010750:Phosphoproteins / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology*
D002147:Calmodulin; D002395:Catecholamines; D010750:Phosphoproteins; D002118:Calcium