Action of tricyclic antidepressants on cyclic AMP in mucosal cells from guinea pig stomach.
In dispersed mucosal cells from guinea pig stomach, tricyclic antidepressants (amitriptyline and imipramine) inhibited the increases in cyclic AMP caused by histamine or dimaprit. The inhibition by low concentrations of amitriptyline was competitive, with a pA2 value of 5.8 +/- 0.15 (Ki, 1.5 +/- 0.8 microM). At high concentrations, amitriptyline reduced the maximal response to histamine as well as inhibited the increase in cyclic AMP caused by theophylline and prostaglandin E1, and also reduced the basal respiratory rate of gastric cells. This inhibition was non-competitive (IC50, 100-250 microM). These results suggest that at low concentrations tricyclic antidepressants interact with the H2-receptors on gastric cells in a fashion similar to their interaction with the brain histamine H2-receptors.
D000527:Alprostadil; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D017259:Dimaprit; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D010101:Oxygen Consumption / Q000187:drug effects; D011458:Prostaglandins E / Q000494:pharmacology; D011968:Receptors, Histamine / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D013890:Thiourea / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D011458:Prostaglandins E; D011968:Receptors, Histamine; D000639:Amitriptyline; D006632:Histamine; D013806:Theophylline; D000242:Cyclic AMP; D000527:Alprostadil; D013890:Thiourea; D017259:Dimaprit