Pertussis-toxin insensitive enkephalin inhibition of adenylyl cyclase in lacrimal acinar cells.
The mechanism by which the inhibitory effect of d-ala2-met-enkephalinamide (DALA) on lacrimal acinar adenylyl cyclase is exerted was assessed in membrane preparations by a cAMP protein binding assay. Inhibition by the analogue was GTP-dependent with a significant enhancement of the inhibitory effect by GTP. While pretreatment of membranes with either cholera or pertussis toxin resulted in stimulation of adenylyl cyclase activity, modification of the Gi alpha subunit by pertussis-toxin catalyzed ADP-ribosylation did not effect the hormonal inhibition of adenylyl cyclase. Incubation of membranes with manganese, however, prevented the inhibitory action of DALA in addition to enhancing basal and forskolin-stimulated adenylyl cyclase activity. The results suggest that the inhibitory effect of DALA in lacrimal acinar cells is exerted via a mechanism other than pertussis-toxin sensitive coupling of the receptor to adenylyl cyclase through Gi. The mechanism may be effected through a pertussis-toxin insensitive G protein, through an interaction with Gi that is pertussis-toxin insensitive, or through an interaction with the catalytic subunit of adenylyl cyclase.
Cripps
M M
MM
Department of Physiology, Louisiana State University Medical Center, New Orleans.
Bennett
D J
DJ
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002712:Chlorides; D002772:Cholera Toxin / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007765:Lacrimal Apparatus / Q000166:cytology / Q000201:enzymology*; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D002712:Chlorides; D017895:Manganese Compounds; D010566:Virulence Factors, Bordetella; D008345:Manganese; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D037342:Pertussis Toxin; C025340:manganese chloride