GTP-binding (G) protein carboxyl methylation controls agonist-induced intracellular Ca2+ response in rat resistance arteries and aortic vascular smooth muscle cells (VSMC).

Carboxyl methylation of the prenylcysteine terminus of G proteins controls receptor-mediated signal transduction in non-vascular tissues. Previous experiments by us with rat arteries have shown that the response to vasoconstrictors such as norepinephrine (NE) was significantly reduced by N-acetyl-S-geranylgeranyl-L-cysteine (AGGC), a specific inhibitor of carboxyl methyl transferase. We therefore studied the effect of AGGC on intracellular Ca2+ (iCa2+) signaling. [iCa2+] was determined (fura-2) in rat resistance arteries (RA, 200 μm diam.) challenged with NE (10−5M), and in vasopressin (AVP)-stimulated rat aortic A10 VSMC. Ethanol and N-acetyl-S-geranyl-L-cysteine (AGC) were used as negative controls. AGGC (5 μM, 30 min. incub.), but not AGC, significantly decreased the iCa2+-response of RA to NE, as well as contraction (m±SEM, Table).