Differential expression of A 2a, A 1-adenosine and D 2-dopamine receptor genes in rat peripheral arterial chemoreceptors during postnatal development

Abstract

The sensitivity of peripheral arterial chemoreceptors in the carotid body to hypoxia increases with postnatal maturation. Carotid sinus nerve activity is augmented by adenosine binding to A 2a-adenosine receptors and attenuated by dopamine binding to D 2-dopamine receptors. In this study, we used in situ hybridization histochemistry to determine the change in the levels of mRNA expression for A 2a and A 1-adenosine receptors and D 2-dopamine receptors in the rat carotid body. We also investigated the cellular distribution and possible colocalization of these receptor mRNAs and tyrosine hydroxylase (TH) mRNAs during the first 2 weeks of postnatal development. By using immunohistocytochemistry, we detected A 2a-adenosine receptor protein in the carotid body and petrosal ganglion. We found that A 2a-adenosine receptor mRNA and protein are expressed in the carotid body in animals at 0, 3, 6 and 14 postnatal days. The level of A 2a-adenosine receptor mRNA expression significantly decreased by 14 postnatal days ( P<0.02 vs. day 0) while D 2-dopamine receptor mRNA levels significantly increased by day 3 and remained greater than D 2-dopamine receptor mRNA levels at day 0 ( P<0.001 all ages vs. day 0). TH mRNA was colocalized in cells in the carotid body with A 2a adenosine receptor and D 2-dopamine receptor mRNAs. A 1-adenosine receptor mRNA was not expressed in the carotid body at any of the ages examined. In the petrosal ganglion, A 1-adenosine receptor mRNA was abundantly expressed in numerous cells, A 2a-adenosine receptor mRNA was expressed in a moderate number of cells while D 2-dopamine receptor mRNA was seen in a few cells in the rostral petrosal ganglion. In conclusion, using in situ hybridization histochemistry, we have shown that mRNA for both the excitatory, A 2a-adenosine receptor, and the inhibitory, D 2-dopamine receptor, is developmentally regulated in presumably type I cells in the carotid body which may contribute to the maturation of hypoxic chemosensitivity. Furthermore, the presence A 1-adenosine receptor mRNAs in cell bodies of the petrosal ganglion suggests that adenosine might also have an inhibitory role in hypoxic chemotransmission.