P2-purinoceptor-activated membrane currents and inositol tetrakisphosphate formation are blocked by suramin.
The effect of suramin on the ATP-induced response in vas deferens DDT1 MF-2 smooth muscle cells was studied. Stimulation of P2-purinoceptors by ATP caused a change in membrane currents, measured by using the whole-cell patch-clamp configuration, and enhanced the formation of inositol phosphates, as analysed by high performance liquid chromatography. The ATP-induced membrane current consisted of a triphasic response, carried by a fast inward current, followed by a transient outward current and a sustained inward current. Inositol tetrakisphosphate (InsP4) formation increased in the presence of ATP. The formation of the isomers Ins(1,3,4,5)P4, Ins(1,3,4,6)P4 and Ins(3,4,5,6)P4 increased significantly after 5 min stimulation with ATP. Suramin inhibited the ATP-evoked membrane currents and the ATP-induced formation of inositol tetrakisphosphate isomers concentration dependently, but did not affect the basal inositol phosphate levels in the absence of ATP. These results indicate that suramin inhibits ATP-activated cellular processes in DDT1 MF-2 vas deferens cells, most likely by acting on P2-purinoceptors.
Hoiting
B
B
Department of Pharmacology and Clinical Pharmacology, University of Groningen, The Netherlands.
Molleman
A
A
Nelemans
A
A
Den Hertog
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D007295:Inositol Phosphates / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000187:drug effects*; D013498:Suramin / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D007295:Inositol Phosphates; D007473:Ion Channels; D011983:Receptors, Purinergic; C081655:inositol-1,3,4,5-tetrakisphosphate; C081653:inositol-1,3,4,6-tetrakisphosphate; C081652:inositol-3,4,5,6-tetrakisphosphate; D013498:Suramin; D000255:Adenosine Triphosphate