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. 1987 Dec;80(6):1755–1762. doi: 10.1172/JCI113268

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

E P Nord 1, M J Howard 1, A Hafezi 1, P Moradeshagi 1, S Vaystub 1, P A Insel 1
PMCID: PMC442450  PMID: 2890661

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 alpha1 adrenergic antagonist completely blocked the NE induced increase in JNa. Clonidine, a partial alpha2 adrenergic agonist, increased JNa by 58 +/- 2% comparable to that observed with NE (10(-5) M). Yohimbine, but not prazosin, inhibited the clonidine-induced increase in JNa, confirming that alpha2 adrenergic receptors were involved. Additional alpha2 adrenergic agents, notably p-amino clonidine and alpha-methyl-norepinephrine, imparted a similar increase in JNa. The clonidine-induced increase in JNa could be completely blocked by the amiloride analogue, ethylisopropyl amiloride (EIPA, 10(-5) M). The transport pathway blocked by EIPA was partially inhibited by Li and cis H+, but stimulated by trans H+, consistent with Na+-H+ antiport. Radioligand binding studies using [3H]prazosin (alpha1 adrenergic antagonist) and [3H]rauwolscine (alpha2 adrenergic antagonist) were performed to complement the flux studies. Binding of [3H]prazosin to the cells was negligible. In contrast, [3H]rauwolscine showed saturable binding to a single class of sites, with Bmax 1678 +/- 143 binding 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 adreno-receptors, 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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