title: Synergistic interaction of muscarinic and opioid receptors with GS-linked neurotransmitter receptors to stimulate adenylyl cyclase activity of rat olfactory bulb.
abstract: 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.
authors.affiliation: Department of Neurosciences, University of Cagliari, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Olianas
authors.forename: P
authors.initials: P
authors.lastname: Onali
mesh_terms: 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
chemical_list: 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