Histamine N-methyltransferase controls the contractile response of guinea pig trachea to histamine.
The contractile response of isolated guinea pig trachea to histamine was potentiated in the presence of the histamine N-methyltransferase (HMT) inhibitor SKF 91488, whereas the diamine oxidase inhibitor aminoguanidine was without effect. SKF 91488 shifted in a concentration-dependent fashion the concentration-response curves to histamine to lower concentrations with the maximum by 1 log unit. The trachea contained significant HMT activity (45.4 +/- 5.0 pmol/min/mg protein). In situ hybridization to detect HMT mRNA indicated that HMT mRNA was present in the epithelium and endothelium, being more abundant in the former. Removal of the epithelium shifted the concentration-response curves to histamine to lower concentrations by 0.8 log unit, and SKF 91488 caused only a slight shift of histamine concentration-response curves in tissues denuded of epithelium. These findings suggest that HMT regulates the contractile response of guinea pig trachea to histamine, and epithelial removal-induced bronchial hyperresponsiveness to histamine is largely explained by the loss of HMT in the epithelium.
Ohrui
T
T
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Yamauchi
K
K
Sekizawa
K
K
Ohkawara
Y
Y
Maeyama
K
K
Sasaki
M
M
Takemura
M
M
Wada
H
H
Watanabe
T
T
Sasaki
H
H
D000818:Animals; D017259:Dimaprit / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D013890:Thiourea / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000201:enzymology
D006146:Guanidines; C024535:SK&F 91488; D006632:Histamine; D006637:Histamine N-Methyltransferase; D013890:Thiourea; C004479:pimagedine; D017259:Dimaprit