The general goal of the applicant laboratory has been to elucidate the mechanisms, kinetics, and regulation of bicarbonate and chloride reabsorption in the rat proximal convoluted tubule (PCT). In particular, the similarities and differences of anion transport in the S1 versus the S2 segments of the PCT have been defined. With respect to bicarbonate transport, the influence on active hydrogen ion secretion and on paracellular bicarbonate permeability by luminal transport determinants (bicarbonate concentration and flow rate), as well as, peritubular factors (bicarbonate concentration and neurohumoral agents) have been assessed. Angiotensin II was discovered to be a potent regulator of S1 PCT acidification. With regard to chloride transport, a systematic assessment has begun of regulation by luminal and peritubular transport determinants. The purposes of the present application are to extend previous investigations into the luminal and peritubular determinants of the active and passive components of bicarbonate and chloride transport in the S1 and S2 PCT of the Munich-Wistar rat. Bicarbonate and chloride, and volume transport rates using in vivo microperfusion and free-flow micropuncture and in vitro receptor analysis microdissected tubules, will be the predominant techniques used to pursue the following specific aims: 1) To examine the type and distribution of adrenoreceptors along the PCT and the adrenergic-selectivity, axial heterogeneity, anion-specificity, mechanisms, kinetics and hormonal-interactions by which neurotransmitters affect PCT transport. 2) To provide additional evidence that S1 PCT bicarbonate absorption can be modulated by neurohumoral agents via changes in intracellular cAMP. 3) To examine the participation by S1 versus S2 cells and the possible role of angiotensin II in the relative or absolute stimulation of PCT bicarbonate transport which occurs during various chronic acid-bases disorders. 4) To examine the active and passive mechanisms and the regulation of chloride absorption in the S1 compared to the S2 PCT.
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