SYNERGISTIC ACTION OF HISTAMINE AND ADENOSINE-TRIPHOSPHATE ON THE RESPONSE TO NORADRENALINE IN RABBIT PULMONARY-ARTERY SMOOTH-MUSCLE CELLS

The interaction between histamine, adenosine triphosphate (ATP) and noradrenaline was studied with the perforated-patch technique in single cells isolated from the rabbit pulmonary artery. In these cells all of the agents activated caffeine-sensitive currents. In potassium-free conditions at a holding potential of -50 mV bath applied histamine, in concentrations that did not produce a response, greatly enhanced the magnitude of inward currents evoked by ionophoretic application of noradrenaline. These inward currents were calcium-activated chloride currents, I-Cl(Ca). In potassium-containing solutions at a holding potential of 0 mV, bath applied histamine potentiated the outward currents (calcium-activated potassium currents (I-K(Ca)) induced by noradrenaline. This synergistic action was rapid in onset, sustained during the continued presence of histamine and reversible. Bath application of noradrenaline inhibited the response to ionophoretically applied noradrenaline but not the caffeine-induced currents. ATP also stimulated I-Cl(Ca) and I-K(Ca) through a mechanism dependent on the caffeine-sensitive intracellular calcium store and also potentiated the currents activated by noradrenaline. It is concluded that one explanation for the phenomenon of potentiation in smooth muscle is convergence of several distinct pharmacological receptors to a common cellular mechanism.