Chemotransduction in the carotid body occurs in specialized type I cells and likely involves a complex series of regulated events which culminates in the release of
neurotransmitter agents and the excitation of afferent nerve fibers. Previous studies have shown that multiple factors, including the levels of
calcium and
cyclic nucleotide second messengers, are important regulators of the chemoreceptor transduction cascade in type I cells. In addition, increases in electrical excitability induced in type I cells by chronic exposure to
hypoxia are mimicked by agents which elevate intracellular
cyclic AMP levels [Stea et al., J Neurosci 1995;15:2192-2202]. These and other findings suggest that
protein kinases, and the phosphorylation of specific
protein targets are important components of the hypoxic transduction machinery. Moreover,
protein kinase-mediated cascades may participate in the well-known physiological adjustments which occur in the carotid body during prolonged stimulation. In the current study, our data demonstrate (1) the presence of specific
protein kinases and target
phosphoproteins in the carotid body, and also in the morphologically similar small intensely fluorescent cells of the superior cervical sympathetic ganglia. (2)
Nitric oxide production and efferent inhibition in the chemosensory tissue is reduced in the presence of the specific
tyrosine kinase inhibitor,
lavendustin A. (3)
Hypoxia-induced
catecholamine release from type I cells is inhibited by the
protein kinase A antagonist,
Rp-cAMPs. And finally (4), exposure to chronic
hypoxia up-regulates the expression of the
tyrosine kinase, fyn, and an important growth regulatory
phosphoprotein, growth associated protein-43 (GAP-43). These findings suggest that second messenger-mediated phosphorylation and dephosphorylation of specific
protein targets is a mechanism capable of regulating diverse cellular functions in the carotid body during acute and chronic stimulation.