MODULATION OF THE PHOSPHOLIPASE-C ACTIVITY IN RAT-BRAIN CORTICAL MEMBRANES BY SIMULTANEOUS ACTIVATION OF DISTINCT MONOAMINERGIC AND CHOLINERGIC MUSCARINIC RECEPTORS
J. Salles et al., MODULATION OF THE PHOSPHOLIPASE-C ACTIVITY IN RAT-BRAIN CORTICAL MEMBRANES BY SIMULTANEOUS ACTIVATION OF DISTINCT MONOAMINERGIC AND CHOLINERGIC MUSCARINIC RECEPTORS, Molecular brain research, 20(1-2), 1993, pp. 111-117
The activation of phospholipase C (PLC) was examined in membranes of r
at cerebral cortex simultaneously exposed to monoaminergic receptor an
d muscarinic receptor agonists after the treatment of membranes with t
wo alkylating agents, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (
100 muM EEDQ) and propylbenzilylcholine (10 nM PrBCM). Treatment of me
mbranes with PrBCM results in a selective inactivation of M3 muscarini
c receptors, while treatment with EEDQ results in a relative sparing o
f M1 muscarinic receptors14. Stimulation of PLC by GTPgammaS alone in
rat cortical membranes had an apparent EC50 of about 0.4 muM, but in t
he presence of carbachol (1 mM) was 0.09 muM. Treatment of rat cortica
l membranes with EEDQ or PrBCM did not modify the concentration-respon
se curves for GTPgammaS alone, but the ability of carbachol (1 mM) to
shift the EC50 of GTPgammaS was lost in PrBCM-treated membranes. We ha
ve previously shown that dopamine, working through D1-like dopamine re
ceptors, alters the PLC response to carbachol by preventing this shift
in the apparent EC50 for GTPgammaS16. When we reproduced these experi
ments in EEDQ- and PrBCM-treated membranes, only in EEDQ-treated membr
anes was dopamine able to inhibit the PLC response to carbachol. The r
esults indicate that the post-receptor mechanisms of PLC activation ar
e distinct for the putative M1 as opposed to M3 muscarinic receptors i
n rat cortical membranes. Further, there appears to be a specific inte
raction between D1 and M3 receptors. 5-Methyltryptamine and carbachol
were used to study the effects of simultaneous activation of the serot
onergic and the putative M1 and M3 muscarinic receptor subtypes, respe
ctively, on PLC activity. In EEDQ-treated membranes, the experimental
data best fit a model for interdependent interactions. In contrast in
PrBCM-treated membranes the data fit a model for independent interacti
on.