SYNERGISTIC INTERACTION OF MUSCARINIC AND OPIOID RECEPTORS WITH G(S)-LINKED NEUROTRANSMITTER RECEPTORS TO STIMULATE ADENYLYL-CYCLASE ACTIVITY OF RAT OLFACTORY-BULB
Mc. Olianas et P. Onali, SYNERGISTIC INTERACTION OF MUSCARINIC AND OPIOID RECEPTORS WITH G(S)-LINKED NEUROTRANSMITTER RECEPTORS TO STIMULATE ADENYLYL-CYCLASE ACTIVITY OF RAT OLFACTORY-BULB, Journal of neurochemistry, 61(6), 1993, pp. 2183-2190
We reported previously that in homogenates of rat olfactory bulb musca
rinic and opioid receptor agonists stimulate adenylyl cyclase activity
. In the present study we show that carbachol (CCh) and Leu-Enkephalin
act synergistically with vasoactive intestinal peptide (VIP) and cort
icotropin-releasing hormone (CRH), but not with l-isoproterenol, in in
creasing cyclic AMP formation. The synergistic interaction consists of
an increase in the maximal adenylyl cyclase activation without a sign
ificant change in the potency of each agonist. CCh also fails to affec
t I-125-CRH binding to olfactory bulb membranes. The synergism require
s micromolar concentrations of GTP. Substitution of the stable GTP ana
log guanosine 5'-O-3'-thiotriphosphate) for GTP allows the CRH stimula
tion, but abolishes the CCh enhancement of both basal and CRH-stimulat
ed enzyme activities. Moreover, in vivo treatment of olfactory bulbs w
ith pertussis toxin completely prevents the muscarinic and opioid effe
cts. Thus, the synergistic interaction appears to result from opioid-
and muscarinic-induced activation of a pertussis toxin-sensitive GTP-b
inding protein which may potentiate the adenylyl cyclase stimulation b
y the stimulatory GTP-binding protein activated by either VIP or CRH r
eceptors.