Synergistic interaction of muscarinic and opioid receptors with GS-linked neurotransmitter receptors to stimulate adenylyl cyclase activity of rat olfactory bulb.
We reported previously that in homogenates of rat olfactory bulb muscarinic 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 corticotropin-releasing hormone (CRH), but not with l-isoproterenol, in increasing cyclic AMP formation. The synergistic interaction consists of an increase in the maximal adenylyl cyclase activation without a significant change in the potency of each agonist. CCh also fails to affect 125I-CRH binding to olfactory bulb membranes. The synergism requires micromolar concentrations of GTP. Substitution of the stable GTP analog guanosine 5'-O-(3'-thiotriphosphate) for GTP allows the CRH stimulation, but abolishes the CCh enhancement of both basal and CRH-stimulated enzyme activities. Moreover, in vivo treatment of olfactory bulbs with pertussis toxin completely prevents the muscarinic and opioid effects. Thus, the synergistic interaction appears to result from opioid- and muscarinic-induced activation of a pertussis toxin-sensitive GTP-binding protein which may potentiate the adenylyl cyclase stimulation by the stimulatory GTP-binding protein activated by either VIP or CRH receptors.
Olianas
M C
MC
Department of Neurosciences, University of Cagliari, Italy.
Onali
P
P
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D004743:Enkephalin, Leucine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009830:Olfactory Bulb / Q000201:enzymology*; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000378:metabolism / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D014660:Vasoactive Intestinal Peptide; D004743:Enkephalin, Leucine; D002217:Carbachol; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol