AJP - Cell Physiology, Vol 265, Issue 6 C1604-C1612, Copyright © 1993 by American Physiological Society
Muscarinic stimulation of gallbladder epithelium. I. Electrophysiology and signaling mechanisms
G. A. Altenberg, M. Subramanyam, J. S. Bergmann, K. M. Johnson and L. Reuss
Department of Physiology, University of Texas Medical Branch, Galveston 77555.
To understand the effects of acetylcholine (ACh) on fluid-absorbing
epithelia, we carried out experiments on Necturus gallbladder epithelium.
Binding studies with 1-quinuclidinyl[phenyl-4(N)-3H]benzilate (QNB)
demonstrated that Necturus gallbladder epithelial cells express
high-affinity muscarinic receptors. The effects of ACh and carbachol were
exerted from the basolateral surface and consisted of a transient
hyperpolarization of both cell membranes and a concomitant decrease in the
apparent fractional resistance of the apical membrane. Atropine blocked
both effects. ACh also elicited transient elevations of inositol
1,4,5-trisphosphate and intracellular free calcium ([Ca2+]i) levels, the
latter by both release from intracellular stores and basolateral influx.
The phospholipase C antagonist U-73122 inhibited the effects of ACh,
whereas inhibition of prostaglandin and guanosine 3',5'-cyclic
monophosphate synthesis with indomethacin or methylene blue, respectively,
had no effect. In conclusion, Necturus gallbladder epithelium expresses
muscarinic receptors in the basolateral membrane. Receptor activation
stimulates phospholipase C and elevates cellular levels of inositol
1,4,5-trisphosphate and [Ca2+]i. The elevation in [Ca2+]i activates K+
channels but apparently not Cl- channels.
