Alpha 2 adrenergic agonists stimulate Na+-H+ antiport activity in the rabbit renal proximal tubule.

Abstract

The role of adrenergic agents in augmenting proximal tubular salt and water flux, was studied in a preparation of freshly isolated rabbit renal proximal tubular cells in suspension. Norepinephrine (NE, 10-5 M) increased sodium influx (JNa) 60±5% above control value. The alpha adrenergic antagonist, phentolamine (10-5 M), inhibited the NE-induced enhanced JNa by 90±2%, while the beta adrenergic antagonist, propranolol, had a minimal inhibitory effect (10±2%). The alpha adrenergic subtype was further defined. Yohimbine (10-5 M), an alpha2 adrenergic antagonist but not prazosin (10-5 M), an alpha, adrenergic antagonist completely blocked the NE induced increase in JN.. Clonidine, a partial alpha2 adrenergic agonist, increased JNS by 58±2% comparable to that observed with NE (10-5 M). Yohimbine, but not prazosin, inhibited the clonidine-induced increase in JN., confirming that alpha2 adrenergic receptors were involved. Additional alpha2 adrenergic agents, notably p-amino clonidine and alpha-methyl-norepinephrine, imparted a similar increase in JN.. The clonidineinduced increase in JNS could be completely blocked by the amiloride analogue, ethylisopropyl amiloride (EIPA, 10'-M). sites/cell and KD 5.4±1.4 nM. In summary, in the isolated rabbit renal proximal tubular cell preparation, alpha2 adrenergic receptors are the predominant expression of alpha adrenoceptors, and in the absence of organic Na'-cotransported solutes, alpha2 adrenergic agonists enhance 22Na influx into the cell by stimulating the brush border membrane Na'-H' exchange pathway.

Renal tubular dopamine outward transfer during Na+‐H+ exchange activation by α1‐ and α2‐adrenoceptor agonists

“…This compares favourably with the evidence that 10 iM EIPA was found to abolish the alkalinization of the cytoplasm observed by activation of a,-and a2-adrenoceptors in rat proximal tubular segments (Gesek & Schoolwerth, 1989). It should be mentioned that EIPA has been chosen because it has been demonstrated to be relatively specific for the inhibition of the proximal luminal Na+-H+ exchanger without significantly interfering with the binding of a-adrenoceptors (Nord et al, 1987). An argument which favours the view that the effects of both phenylephrine and quinoxaline are mediated through the activation of, al-and a2-adrenoceptors respectively, is that on the selective antagonism of their effects.…”

“…The antinatriuretic action resulting from the stimulation of renal tubular M2-adrenoceptors is believed to be dependent on the activation of the Na+-H+ exchanger (Insel et al, 1985;Nord et al, 1987; and would involve inhibition of the enzyme adenylate cyclase (Pettinger et al, 1987); on the other hand, dibutyryl cyclic AMP has been demonstrated to inhibit Na+-H+ exchanger activity (Kahn et al, 1985;Weinman et al, 1987). The results presented here show that the facilitatory effect of quinoxaline can, in fact, be reversed by dibutyryl cyclic AMP and forskolin, an activator of the enzyme adenylate cyclase, but not by (+ )-sphingosine, the PKC inhibitor.…”

“…The aim of the present work was to evaluate the role of the Na+-H+ exchanger on the renal outward transport of dopamine; the results described here are on the effects of inhibitors (amiloride and EIPA; Vigne et al, 1984) and activators (quinoxaline and phenylephrine; Nord et al, 1987;Gesek & Schoolwerth, 1989; of the Na+-H+ exchanger on the outflow of dopamine in rat kidney slices loaded with L-DOPA. A preliminary account of some these findings has been presented previously (Soares-da-Silva, 1992b (Sokal & Rolhf, 1981 Figure 1, this effect was significantly more marked for EIPA than for amiloride; the ICm value for EIPA was 5.6 ± 0.3 l.M.…”

Renal effects of infusion of rilmenidine and guanabenz in conscious dogs: contribution of peripheral and central nervous system α2–adrenoceptors

“…Guanabenz and rilmenidine also reduced sodium excretion in dogs with intact autonomic reflexes. This effect is probably mediated directly within the renal tubule, where activation of 0(2-adrenoceptors enhances Na' transport (Nord et al, 1987). The lack of an antinatriuretic effect of these agents in ganglion-blocked dogs probably reflects the competing influences of this direct antinatriuretic influence and the natriuretic influence of increased arterial pressure (see Anderson et al, 1995).…”

“…Because a natriuretic effect of guanabenz could conceivably take some time to develop, we also tested the effects of infusing a low dose (5 jig kg-' plus 0.2 jg kg-' min-) over a 90 min period, which also had no effect on sodium excretion. We also reasoned that a natriuretic effect of activation of putative 12-binding sites by guanabenz might be opposed by the antinatriuretic effects of the drug mediated by activation of tubular a2-adrenoceptors (see Nord et al, 1987). However, following blockade of ac2-adrenoceptors by 2-methoxyidazoxan (15 jig kg-' plus 0.6 jig kg-' min-'), guanabenz (10-100 jg kg-') still had no natriuretic effect.…”