Metabolism and actions of ADP-riboses in coronary arterial smooth muscle.
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 micrograms protein for ADPR and 1.37 +/- 0.03 nmol/min/100 micrograms protein for cADPR. In patch clamp experiments, ADPR produced a concentration-dependent increase in the activity of a calcium activated K (Kca) channel in inside-out membrane patches of coronary arterial smooth muscle cells at concentrations of 0.1, 1 and 10 microM. The open state probability (NPo) of Kca channel was maximally increased 5-fold at a concentration of 10 microM. cADPR reduced the activity of Kca channel at concentrations of 1 and 10 microM. 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 Kca channel in vascular smooth muscle cells.
Li
P
P
Department of Pharmacology, Medical College of Wisconsin, Milwaukee 53226, USA.
Zou
A P
AP
Campbell
W B
WB
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D036563:Cyclic ADP-Ribose; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009243:NAD / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D014665:Vasodilator Agents; D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose