Metabolism and Actions of ADP-Riboses in Coronary Arterial Smooth Muscle

Abstract

The present study examined the metabolism of ADP-ribose (ADPR) and cyclic ADP-ribose (cADPR) in small bovine coronary arterial homogenates and characterized the effects of these nucleotides on the activity of potassium (K⁺) channels in coronary smooth muscle cells. ADPR and cADPR were produced from NAD+ (lmM) by homogenates from small bovine coronary arteries. The conversion rate was 2.81 ± 0.19 nmol/min/100 µg protein for ADPR and 1.37 ± 0.03 nmol/min/100 µg protein for cADPR. In patch clamp experiments, ADPR produced a concentration-dependent increase in the activity of a calcium activated K (K_Ca) channel in inside-out membrane patches of coronary arterial smooth muscle cells at concentrations of 0.1, 1 and 10 µM. The open state probability (NPo) of KCa channel was maximally increased 5-fold at a concentration of 10 µM. cADPR reduced the activity of K_Ca channel at concentrations of 1 and 10 µM. The NPo was decreased by 45% and 75%, respectively. The results indicate that there is an enzymatic pathway in the coronary arterial smooth muscle to produce ADPR and cADPR. These nucleotides may play a role in the control of coronary vascular tone by altering the activity of the K_Ca channel in vascular smooth muscle cells.