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1 Departments of Anesthesiology, and Physiology and Biophysics, Mayo Clinic and Foundation, Rochester 55905; 3 Department of Veterinary PathoBiology, University of Minnesota, St. Paul, Minnesota 55108; and 2 Department of Pulmonary Diseases, University Hospital Nijmegen, Nijmegen, The Netherlands NL6500 HB
Received 23 September 1996; accepted in final form 3 February 1997.
Prakash, Y. S., H. F. M. van der Heijden, M. S. Kannan, and
G. C. Sieck. Effects of salbutamol on intracellular calcium oscillations in porcine airway smooth muscle. J. Appl.
Physiol. 82(6): 1836-1843, 1997.
Relaxation of
airway smooth muscle (ASM) by
-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
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 µM. 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
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.
2-adrenoceptor agonists; confocal imaging; asthma; calcium channel; calcium efflux
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