Hormonal interactions with the proximal Na(+)-H+ exchanger

Various types of catecholamine and peptide hormone receptors have been localized to the renal cortex, with the majority of these binding sites located on the proximal tubule. Both subtypes of alpha-adrenergic receptors, angiotensin II (ANG II), parathyroid hormone (PTH), and dopamine (DA) DA-1 receptors have all demonstrated binding sites on this nephron segment. One- to two-thirds of Na+ transport in the proximal nephron is proposed to be mediated by a Na(+)-H+ exchanger. Each of these hormones has been shown to alter Na(+)-H+ exchange activity. The purpose of this study was to examine the interactions of these various hormones on proximal nephron Na(+)-H+ exchange at both physiological and pharmacological concentrations. Na(+)-H+ exchange activity was determined in isolated rat proximal segments by assessing the uptake of 22Na+ that was suppressible by the Na(+)-H+ exchange inhibitor, ethylisopropylamiloride (EIPA). Time course studies indicated that a 1-min preincubation with the hormones followed by a 1-min exposure to 22Na+ was necessary to achieve a steady-state EIPA-suppressible 22Na+ uptake. Selective alpha-adrenergic agonists produced a maximum stimulation of 22Na+ uptake at approximately 10(-6) M final concentration (less than or equal to 192% above the control level of uptake); ANG II produced a maximum increase at 10(-12) M (an 82% increase above the control level). In contrast, PTH and DA inhibited 22Na+ uptake most effectively at 10(-8) M and 10(-6) M, respectively. When submaximal (10(-9) M) concentrations of alpha-agonists were incubated in combination with ANG II, a synergistic effect was observed only with selective alpha 2-agonists.(ABSTRACT TRUNCATED AT 250 WORDS)