Key result
In rat glomeruli, P2Y1, P2Y2, P2Y4, and P2Y6 receptor mRNAs were detected, but sympathectomy did not affect ATP-induced inositol phosphate production.
The study identifies specific P2Y receptor subtypes in rat glomeruli and suggests intra-renal sympathetic nerve terminals are not the primary source of extracellular ATP.
Sympathectomy leaves ATP signaling intact in rat glomeruli; leaves open non-neuronal ATP sources and P2Y receptor roles in human kidney disease.
Extracellular ATP can mobilize intracellular calcium in rat glomeruli by interacting with P2Y receptors. However, the identity of the receptor subtypes involved is not known. In the present study, we have used RT-PCR to identify mRNAs for specific P2Y receptor subtypes expressed in the rat glomerulus: mRNA for P2Y1, P2Y2, P2Y4 and P2Y6 receptors was detected. Functional expression of P2Y1 and P2Y2/P2Y4, but not P2Y6, receptors in intact glomeruli was confirmed by measuring the relative stimulation of the inositol phosphate pathway induced by selective agonists of a particular receptor subtype. Finally, we have used available polyclonal antibodies to confirm the expression of P2Y1 and P2Y2 in the glomerulus, in mesangial cells and glomerular epithelial cells (podocytes), respectively; but we could not demonstrate P2Y4 or P2Y6 receptor expression by this means. In a separate series of experiments, we have examined the possibility that intra-renal sympathetic nerve terminals are a source of extracellular ATP and that this would be supported, though not excluded, by supersensitivity to ATP following denervation. Nucleotide-induced stimulation of the inositol phosphate pathway was measured in both control rats and rats that had been sympathectomized by intraperitoneal injection of 6-hydroxydopamine. The response to norepinephrine was measured as a positive control. In the sympathectomized rats, the effect of norepinephrine was significantly enhanced, whereas ATP-induced inositol phosphate production was unaffected, being similar in both groups of animals.
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Bailey et al. (2004) studied this question. Sympathectomy by intraperitoneal injection of 6-hydroxydopamine vs. Control rats was evaluated on Nucleotide-induced stimulation of the inositol phosphate pathway. In rat glomeruli, P2Y1, P2Y2, P2Y4, and P2Y6 receptor mRNAs were detected, but sympathectomy did not affect ATP-induced inositol phosphate production.
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