Possible participation of histamine H3-receptors in the regulation of anaphylactic histamine release from isolated rat peritoneal mast cells.
Anaphylactic histamine release from isolated rat peritoneal mast cells was concentration-dependently blocked by a 5-min treatment with exogenous histamine at 0.9 and 9 microM and enhanced by a 20- to 30-min treatment with thioperamide (H3-antagonist) at 3 microM with significance, but little affected by mepyramine (H1-antagonist) and cimetidine (H2-antagonist) at the cell concentration of 10(6) mast cells/ml. At a low concentration of mast cells (10(4) mast cells/ml), (R)-alpha-methylhistamine (alpha-MH), an H3-agonist, at 0.9-90 microM also inhibited the release in a concentration-dependent fashion. Thioperamide, but neither mepyramine nor cimetidine, significantly restored the decreased release by alpha-MH. However, the complete restoration by thioperamide could not be achieved because the drug itself slightly but concentration-dependently inhibited anaphylactic histamine release. On the other hand, not only betahistine and dimaprit but also alpha-MH did not suppress histamine release from the mast cells induced by compound 48/80. In rat plasma, considerable levels of histamine were detected. From these results, it is strongly suggested that histamine H3-like receptors are largely responsible for the negative feedback regulation of the anaphylactic histamine release from rat peritoneal mast cells.
Kohno
S
S
Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
Nakao
S
S
Ogawa
K
K
Yamamura
H
H
Nabe
T
T
Ohata
K
K
D000707:Anaphylaxis / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine / Q000494:pharmacology; D017259:Dimaprit / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000097:blood* / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology*; D006633:Histamine Antagonists; D006636:Histamine Release; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008761:Methylhistamines / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000502:physiology*; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity
D000927:Anticonvulsants; D017442:Histamine Agonists; D006633:Histamine Antagonists; D008761:Methylhistamines; D010880:Piperidines; D018100:Receptors, Histamine H3; D003189:p-Methoxy-N-methylphenethylamine; C069357:alpha-methylhistamine; D002927:Cimetidine; D006632:Histamine; D007770:L-Lactate Dehydrogenase; D011738:Pyrilamine; C052075:thioperamide; D017259:Dimaprit