Chronic MAO A and MAO B inhibition decreases the 5-HT1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase.
The effect of chronic administration of various monoamine oxidase (MAO) inhibitors on the ability of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to inhibit forskolin-stimulated adenylate cyclase activity was studied. Groups of 12 rats were given either saline, (E)-beta-fluoromethylene-m-tyrosine (MDL 72394 0.25 mg/kg p.o.), clorgyline (1 mg/kg p.o.), selegiline (1 mg/kg p.o.) or tranylcypromine (5 mg/kg p.o.) once a day for 21 days. Biochemical determinations were made 72 h after the final dose. MDL 72394 and tranylcypromine produced a nonselective inhibition of MAO but clorgyline and selegiline selectively inhibited MAO A and MAO B respectively. All treatments that inhibited MAO A also increased tissue levels of 5-HT. Chronic treatment with MDL 72394, clorgyline or tranylcypromine reduced the ability of 8-OH-DPAT to inhibit forskolin-stimulated adenylate cyclase activity. These data suggest that chronic nonselective and chronic MAO A inhibition causes a down-regulation of the 5-HT1A-mediated inhibition of forskolin-stimulated adenylate cyclase activity.
Sleight
A J
AJ
Merrell Dow Research Institute, Strasbourg Center, France.
Marsden
C A
CA
Palfreyman
M G
MG
Mir
A K
AK
Lovenberg
W
W
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D014191:Tranylcypromine / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D008996:Monoamine Oxidase Inhibitors; D011985:Receptors, Serotonin; D005576:Colforsin; D014191:Tranylcypromine; D014443:Tyrosine; C046880:beta-fluoromethylene-3-tyrosine; D000262:Adenylyl Cyclases; D003010:Clorgyline