Histamine N-methyltransferase regulates histamine-induced phosphoinositide hydrolysis in guinea pig cerebellum.
We report here that the dose-response curve of the histamine-stimulated phosphoinositide hydrolysis in the guinea pig cerebellar slices was shifted to the left when the slices were pretreated with SKF 91488 (100 microM), a specific inhibitor of histamine N-methyltransferase (HMT). In contrast, the pretreatment of the cerebellar slices with aminoguanidine (100 microM - 1 mM), an inhibitor of diamine oxidase, had no effect on histamine-induced phosphoinositide hydrolysis. HMT mRNA was expressed abundantly in cerebellum, especially in Purkinje cells. These observations suggest that HMT regulates histaminergic neurotransmission in guinea pig cerebellum more predominantly than diamine oxidase in histamine degradation.
Kitanaka
J
J
Department of Pharmacology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Hyogo, Japan.
Kitanaka
N
N
Tsujimura
T
T
Terada
N
N
Takemura
M
M
D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D017259:Dimaprit / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+); D005993:Glycerolphosphate Dehydrogenase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006637:Histamine N-Methyltransferase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D006868:Hydrolysis / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000494:pharmacology; D009924:Organ Culture Techniques; D010716:Phosphatidylinositols / Q000378:metabolism* / Q000493:pharmacokinetics; D012313:RNA / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014316:Tritium / Q000493:pharmacokinetics
D006633:Histamine Antagonists; D015345:Oligonucleotide Probes; D010716:Phosphatidylinositols; D014316:Tritium; C024535:SK&F 91488; D012313:RNA; D006632:Histamine; D005993:Glycerolphosphate Dehydrogenase; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+); D006637:Histamine N-Methyltransferase; D017259:Dimaprit