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Angiotensin II-Induced Activation of Na⁺-H⁺ Exchange in Adrenal Glomerulosa Cells Is Mediated by Protein Kinase C^*

Endocrine-Hypertension Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School Boston, Massachusetts 02115

Address requests for reprints and all correspondence to: Paul R. Conlin, M.D., Endocrine-Hypertension Division, Brigham and Women’s Hospital, 221 Longwood Ave., Boston, MA 02115.

Abstract

Modulation ofNa⁺-H⁺exchange (Na/H EXCH) by hormones and growth factors may be important in cell growth. We have previously shown that Na/H EXCH in adrenal glomerulosa cells is activated by angiotensin II (ANG II), a potent stimulator of aldosterone secretion. In the present paper, we have investigated the role of protein kinase C (PKC) in the activation of Na/H EXCH by ANG II. To accomplish this, we monitored cytosolic pH (pH_i) in cells loaded with 2,7-bisearboxyethyl- 5(6)-carboxyflourescein and measured initial rates of ²²Na uptake into glomerulosa cells in the presence or absence of dimethylamiloride. Both phorbol 12-myristate 13-acetate (PMA) and ANG II increased the activity of Na/H EXCH similarly when studied under basal conditions (pH_i 7.1). This was accompanied by alkalinization of pH_i and an increase in dimethylamiloride-sensitive Na⁺ influx. Study of kinetics of the antiporter activation showed that both ANG II and PMA led to an increase in the maximal rate (V_max) and a decrease in the Michaelis-Menten constant (K_m) for external Na⁺. The pH_i dependence of Na⁺ influx was half-maximal (pK) at pH, 7.09 and remained unchanged in the presence of ANG II (pK 7.03) and PMA (pK 7.14). Depleting the cells of PKC by exposing them to PMA (1 µM) for 3 h caused a marked reduction in control and ANG II-stimulated Na+ influx and control pK (7.09 to 6.85, P < 0.05). However, with PKC depletion, the kinetics of Na/H EXCH (V_max K_m for external Na⁺ and pK) were unaffected by ANG II. Thus, Na/H EXCH in adrenal glomerulosa cells functions under basal conditions, and its relatively alkaline pK (7.09) is dependent upon PKC activity. In addition, the ANG II-induced activation of Na/H EXCH is modulated by PKC. These effects suggest an important role for PKC in pH_i regulation of adrenal glomerulosa cells, particularly during ANG II stimulation of aldosterone secretion. (Endocrinology 129: 1861–1868, 1991

Footnotes

^* This work was supported by NIH Grants RR-02635 and HL-42120 and a Specialized Center of Research (SCOR) in Hypertension Grant HL-36568

Received April 1, 1991.

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