Effects of salbutamol on intracellular calcium oscillations in porcine airway smooth muscle

Relaxation of airway smooth muscle (ASM) by β-adrenoceptor agonists involves reduction of intracellular Ca²⁺ concentration ([Ca²⁺](i)). In porcine ASM cells, acetylcholine induces [Ca²⁺](i) oscillations that display frequency modulation by agonist concentration and basal [Ca²⁺](i). We used real-time confocal microscopy to examine the effect of salbutamol (1 nM to 1 μM), a β₂-adrenoceptor agonist, on [Ca²⁺](i) oscillations in freshly dissociated porcine ASM cells. Salbutamol decreased the frequency of [Ca²⁺](i) oscillations in a concentration-dependent fashion, completely inhibiting the oscillations at 1μM. These effects were mimicked by a cell- permeant analog of adenosine 3',5'-cyclic monophosphate. The inhibitory effect of salbutamol was partially reversed by BAY K 8644. Salbutamol reduced [Ca²⁺)(i) even when sarcoplasmic reticulum (SR) Ca²⁺ reuptake and Ca²⁺ influx were blocked. Lanthanum blockade of Ca²⁺ efflux attenuated the inhibitory effect of salbutamol on [Ca²⁺](i). The [Ca²⁺](i) response to caffeine was unaffected by salbutamol. On the basis of these results, we conclude that β₂-adrenoceptor agonists have little effect on SR Ca²⁺ release in ASM cells but reduce [ Ca²⁺](i) by inhibiting Ca²⁺ influx through voltage-gated channels and by enhancing Ca²⁺ efflux.