LOCALIZATION AND FUNCTIONAL-EFFECTS OF ADENOSINE A(1) RECEPTORS ON CARDIAC VAGAL AFFERENTS IN ADULT RATS

Middlekauff, Holly R., Scott A. Rivkees, Helen E. Raybould, Melo Bitti caca, Joshua I. Goldhaber, and James N. Weiss. Localization and functi onal effects of adenosine A(l) receptors on cardiac vagal afferents in adult rats. Am. J. Physiol. 274 (Heart Circ. Physiol. 43): H441-H447, 1998. -There is evidence to suggest that during ischemia adenosine ac ts on cardiac vagal afferent neurons to activate systemic reflexes and to modulate cardiac nociception. The purpose of this study was to det ermine whether adenosine receptors are present and have direct cellula r electrophysiological actions on cardiac vagal afferent neurons. In r adioreceptor assays of nodose ganglion tissue from rats, binding was d etectable for A(1) (39.6 +/- 1.2 fmol/mg protein) but not A(2a), adeno sine receptors. These findings were confirmed using the complementary approach of receptor-labeling autoradiography. Using in situ hybridiza tion we saw specific labeling over similar to 50% of neurons in the no dose ganglia, but not over nonneuronal cells. In colabeling studies, c ardiac vagal afferent neurons were identified by retroneuronal labelin g with fluororuby. Of cardiac vagal afferents approximately one-half w ere strongly positive for A(1) adenosine receptors (immunocytochemistr y). In patch-clamping experiments, adenosine inhibited peak inward cal cium current in 7 of 11 cells by 48 +/- 13%. In conclusion, adenosine A(1) receptors reside on a subset of vagal afferent neurons, including cardiac vagal afferents, and have electrophysiological effects that m odulate neuroexcitability in cultured nodose ganglion neurons.