Alpha-adrenoceptor stimulation by norepinephrine increases Na-Ca exchange in rabbit abdominal aorta, likely mediated through protein kinase C activation.
Alpha-adrenergic PKC-mediated Na-Ca exchange stimulation is supported in rabbit aorta; leaves open human relevance and therapeutic translation.
Na-Ca exchange was measured as intracellular Na+ (Na+i)-dependent 45Ca uptake in rabbit abdominal aortic rings. The amount of Na+i-dependent 45Ca uptake was proportional to both the concentration of Na+ in the Na(+)-loading solution and the concentration of Ca2+ in the assay medium. Na+i-dependent 45Ca uptake was inhibited by incorporation of Na+ in the assay medium and by amiloride analogues. Norepinephrine significantly enhanced the rate of 45Ca uptake in Na(+)-loaded tissue but had no effect on Na+i-independent 45Ca uptake. The effect of norepinephrine was prevented by phentolamine but not by propranolol. The stimulatory effect of norepinephrine was absent when the concentration of extracellular Ca2+(Ca2+o) was 0.3 mM or lower but became significant at 0.6 mM and higher. Na-Ca exchange was also increased by phorbol 12,13-dibutyrate but not by its inactive analogue (4 alpha-phorbol 12,13-didecanoate). 1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, blocked the stimulatory effect of norepinephrine on Na-Ca exchange. It is suggested that alpha-adrenoceptor stimulation increases Na-Ca exchange in rabbit abdominal aorta in a Na+i- and Ca2+o-dependent fashion. This effect is possibly mediated through the activation of protein kinase C.
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Khoyi et al. (1991) studied this question.
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