Effects of salbutamol on intracellular calcium oscillations in porcine airway smooth muscle.
Relaxation of airway smooth muscle (ASM) by beta-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 microM), a beta 2-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 1 microM. 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 beta 2-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.
Prakash
Y S
YS
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
van der Heijden
H F
HF
Kannan
M S
MS
Sieck
G C
GC
D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism*; D009991:Oscillometry; D009994:Osmolar Concentration; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013552:Swine; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000109:Acetylcholine; D000420:Albuterol; D002118:Calcium