Ca(2+) influx through nonselective cation channels plays an essential role in noradrenaline-induced arachidonic acid release in Chinese hamster ovary cells expressing alpha(1A)-, alpha(1B)-, or alpha(1D)-adrenergic receptors.

We constructed Chinese hamster ovary (CHO) cells stably expressing alpha(1A)-, alpha(1B)-, or alpha(1D)-adrenergic receptors (CHO-alpha(1A), CHO-alpha(1B), or CHO-alpha(1D), respectively) and compared the Ca(2+) channels activated by noradrenaline (NA) in these cells using whole-cell recordings and monitoring of the intracellular free Ca(2+) concentration ([Ca(2+)](i)). We also investigated the involvement of Ca(2+) channels in the NA-induced arachidonic acid release. In all three cell types, NA at concentrations > or =10 nM induced a sustained increase in [Ca(2+)](i) attributable to extracellular Ca(2+) influx in [Ca(2+)](i) monitoring and an inward current in whole-cell recording. The current-voltage relationships were linear, and their reversal potentials were close to 0 mV. The reversal potential of the currents was not affected by a change in the concentration of Cl(-) in the bath solution. Moreover, a current could be induced in a bath solution containing only Ca(2+) as the movable cation. LOE 908, a receptor-operated Ca(2+) channel blocker, inhibited the sustained increase in [Ca(2+)](i) and inward currents in a concentration-dependent manner, and complete inhibition was observed at concentrations > or = 3 microM. NA induced arachidonic acid release in all three cell types. This release was entirely dependent on extracellular Ca(2+) influx. Moreover, LOE 908 at concentrations > or = 3 microM blocked the NA-induced increase in arachidonic acid release. These results indicate that 1) NA activates LOE 908-sensitive Ca(2+)-permeable nonselective cation channels (NSCCs) in CHO-alpha(1A), CHO-alpha(1B), and CHO-alpha(1D), and 2) the Ca(2+) influx through NSCCs may play an important role in the NA-induced enhancement of arachidonic acid release in these cells.