Effects of histamine H3 receptor agonist and antagonist on histamine co-transmitter expression in rat brain.
The histaminergic H3-receptor (H3R) controls histamine synthesis and release in the tuberomamillary nucleus. We evaluated the effects of stimulating or blocking of H(3)R on glutamate-decarboxylase 67 kDa (GAD-67) and galanin mRNA expression, two histamine co-transmitters.After in situ hybridization histochemistry (ISHH), we observed a colocalization of 100% between histidine decarboxylase (HDC) and GAD-67 or H3R and of 80 to 97% with galanin. Adult rats received an H3R agonist ((R)alpha-Methylhistamine) or antagonist (ciproxifan) and were sacrificed 1 or 3 hours later. Treatment effects on HDC, galanin and GAD-67 mRNA were studied by quantitative ISHH on serial sections. Treatment with the H3R agonist known to decrease histamine neuron activity initially reduced HDC and galanin gene expression but an inverse change, presumably reflecting a compensatory mechanism, was observed after 3 h on both markers. In contrast, the H3R antagonist known to activate histamine neurons, had opposite effects on the two markers, suggesting that co-transmitters are submitted to independent control mechanisms. Furthermore, GAD-67 mRNA levels were not significantly modified by these treatments.
Chotard
C
C
Unité INSERM U109 de Neurobiologie et Pharmacologie Moléculaire, Centre Paul Broca, Paris, France.
Ouimet
T
T
Morisset
S
S
Sahm
U
U
Schwartz
J C
JC
Trottier
S
S
D000818:Animals; D019004:Galanin / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000235:genetics; D006632:Histamine / Q000096:biosynthesis*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000235:genetics; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D007527:Isoenzymes; D008761:Methylhistamines; D012333:RNA, Messenger; D018100:Receptors, Histamine H3; D005680:gamma-Aminobutyric Acid; C115705:ciproxifan; C069357:alpha-methylhistamine; D006632:Histamine; D019004:Galanin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D006640:Histidine Decarboxylase