ALPHA-ADRENERGIC RECEPTORS REGULATE HUMAN LYMPHOCYTE AMILORIDE-SENSITIVE SODIUM-CHANNELS

Two independent signal transduction pathways regulate lymphocyte amilo ride-sensitive sodium channels (ASSCs), one utilizing cAMP as a second messenger and the other utilizing a GTP-binding protein. This implies that two plasma membrane receptors play a role in the regulation of l ymphocyte ASSCs. In this study, we tested the hypothesis that alpha(1) - and az-adrenergic receptors independently regulate lymphocyte ASSCs via the two previously identified second messengers. Direct measuremen ts indicated that norepinephrine increased lymphocyte cAMP and activat ed ASSCs. The alpha(2)-specific inhibitor, yohimbine, blocked this act ivation, thereby linking alpha(2)-adrenergic receptors to ASSC regulat ion via cAMP. The alpha(1)-specific ligand, terazosin, acted as an ago nist and activated lymphocyte ASSCs but inhibited ASSC current that ha d been preactivated by norepinephrine or 8-(4-chlorophenylthio) (CPT)c AMP. Terazosin had no effect on the lymphocyte whole cell ASSC current s preactivated by treatment with pertussis toxin. This finding indirec tly links alpha(1)-adrenergic receptors to lymphocyte ASSC regulation via GTP-binding proteins. Terazosin had no direct inhibitory or stimul atory effects on alpha,beta,gamma-endothelial sodium channels reconsti tuted into planar lipid bilayers and expressed in Xenopus oocytes, rul ing out a direct interaction between terazosin and the channels. These findings support the hypothesis that both alpha(1)- and alpha(2)-adre nergic receptors independently regulate lymphocyte ASSCs via GTP-bindi ng proteins and cAMP, respectively.