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+ (1mM) 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 K(Ca) 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.