The overall objective of this research proposal is to study the possible role of neurotransmitters in the regulation of renal tubular fluid reabsorption. Simultaneous microperfusions of peritubular capillaries and tubular lumen will be used to examine the effects of neurotransmitters on fluid absorption in both proximal and distal convoluted tubules of the rat kidney. We will identify which segment of the nephron is affected by which transmitter and then, determine whether the neurotransmitter acts from the basolateral side or from the luminal side of the tubule cell. We will further characterize the receptor mechanisms of neurotransmitters action by using specific antagonists for alpha and beta adrenergic, dopaminergic and cholinergic receptors. The """"""""Yin Yang Hypothesis"""""""", or the possible opposing influence of cyclic GMP and cyclic AMP, in the mediating of cellular action of neurotransmitters will be tested. The results obtained from in situ microperfusion studies will be correlated with those obtained from in vitro studies on isolated tubular cell preparations. The change of cellular nucleotide concentration in response to the addition of neurotransmitters will be examined in isolated tubular cell preparations. The role of calcium ion in the neurotransmitter mediated activation of cyclic nucleotides will also be investigated. Information obtained from this research will permit us to define possible mechanisms of neural control of renal function.
