The activity of amitriptyline as a differential inhibitor of amine secretion from rat peritoneal mast cells: the contribution of amine uptake.
Amitriptyline, at a concentration of 10(-4) M, significantly inhibited the release of histamine from purified peritoneal rat mast cells in response to compound 48/80, but was without effect upon the output of 5-HT. The reduction was not extensive, and concentrations of the drug above or below 10(-4) M were without effect. Amitriptyline (10(-8)-10(-4) M) inhibited uptake of exogenous 5-HT in a concentration dependent manner. Paradoxically, however, histamine uptake was significantly increased in the presence of this drug, but only at a concentration of 10(-4) M. This effect was observed at 4 degrees C for both amines. Concentrations of amitriptyline in excess of 10(-4) M caused lysis of the mast cells. These results suggest that the observed selective inhibitory effect of amitriptyline upon histamine output may be a function of altered amine uptake rather than differential inhibition and 5-HT secretion.
Purcell
W M
WM
Hatfield Polytechnic, Herts, UK.
Hanahoe
T H
TH
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D001679:Biogenic Amines / Q000378:metabolism*; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D001679:Biogenic Amines; D000639:Amitriptyline; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine