ETHANOL DISRUPTS CARBAMYLCHOLINE-STIMULATED RELEASE OF ARACHIDONIC-ACID FROM CHINESE-HAMSTER OVARY CELLS EXPRESSING DIFFERENT SUBTYPES OF HUMAN MUSCARINIC RECEPTOR
Sm. Stair et al., ETHANOL DISRUPTS CARBAMYLCHOLINE-STIMULATED RELEASE OF ARACHIDONIC-ACID FROM CHINESE-HAMSTER OVARY CELLS EXPRESSING DIFFERENT SUBTYPES OF HUMAN MUSCARINIC RECEPTOR, Alcoholism, clinical and experimental research, 22(2), 1998, pp. 409-415
Ethanol disrupts signal transduction mediated by a variety of G-protei
n coupled receptors, We examined the effects of ethanol on arachidonic
acid release mediated by muscarinic acetylcholine receptors, Chinese
hamster ovary (CHO) cells transfected with the different subtypes of h
uman muscarinic receptors (M1 to M5) were incubated with [H-3]arachido
nic acid ([H-3]AA) for 18 hr, washed, and exposed to the cholinergic a
gonist carbamylcholine for 15 min. Carbamylcholine induced [H-3]AA rel
ease from CHO cells expressing M1, M3, or M5, but not M2 or M4, muscar
inic receptors, Dose response curves revealed that carbamylcholine sti
mulated [H-3]AA release by up to 12-fold with an EC50 of approximate t
o 0.4 mu M; maximal responses were obtained with 10 mu M carbamylcholi
ne, Exposure of M1-, M3-, or M5- expressing cells to ethanol for 5 min
before stimulating with carbamylcholine reduced [H-3]AA release by 40
to 65%; 50% of the maximal inhibition was obtained with an ethanol co
ncentration of 30 to 50 mM, Ethanol did not affect basal [H-3]AA relea
se measured in the absence of carbamylcholine, Dose response curves su
ggest that ethanol acts as a noncompetitive inhibitor of muscarinic re
ceptor-induced [H-3]AA release insofar as maximal [H-3]AA release was
depressed in the presence of ethanol with no apparent change in the EC
50 for stimulation by carbamylcholine, Exposure of CHO cells to 38 mM
ethanol for 48 hr increased [H-3]AA release induced by carbamylcholine
without affecting basal [H-3]AA release or altering the EC50 for carb
amylcholine, These results indicate that ethanol acutely inhibits musc
arinic receptor signaling through the arachidonic acid pathway in a no
ncompetitive manner, but chronically enhances muscarinic signaling thr
ough the same pathway.