Characterization of histaminergic H3 receptors in intraocular tuberomammillary transplants containing histaminergic neurons.

This study was performed to investigate the physicological properties of histaminergic neurons in intraocular hypothalamic transplants. Pieces of posterolateral hypothalamus containing the tuberomammillary nucleus were dissected from Embryonic Day 17 rat fetuses and transplanted into the anterior chamber of the eye of adult rat hosts. The hypothalamic transplants were left to mature for 2-5 months, after which in vivo electrophysiological recordings were performed. Extracellular recordings revealed spontaneously active neurons in the grafts, with a mean (+/- SEM) firing rate of 2.8 +/- 2.0 Hz and a mean action potential duration of 1.2 +/- 0.5 ms. When the surface of the grafts was superfused with histamine, the neuronal activity was depressed at concentrations above 30 microM. Superfusion with the H3 agonist (R)-alpha-methylhistamine also elicited depression of baseline firing rate, with an EC50 of 0.435 microM. This depression could be antagonized by superfusion with the H3-receptor antagonist thioperamide. In studies of histamine levels using a sensitive radioenzymatic assay, the mean (+/- SEM) level of histamine in the grafts was 73 +/- 28 ng/g tissue, i.e., about half the concentration of histamine in the adult rat hypothalamus in situ. Intracellular recordings in combination with biocytin labeling and histidine decarboxylase immunohistochemistry suggested that the grafted neurons from which recordings were made were histaminergic. Taken together, these data indicate that tuberomammillary neurons continue their development in intraocular transplants and develop physiological characteristics found in these neurons in situ.

pros-methylimidazoleacetic acid in rat brain: its regional distribution and relationship to metabolic pathways of histamine.

pros-Methylimidazoleacetic acid (p-MIAA; 1-methylimidazole-5-acetic acid), an isomer of the histamine metabolite, tele-methylimidazoleacetic acid (t-MIAA), is present in brain and CSF. Its relationship to histamine synthesis and catabolism was assessed in brains of rats. p-MIAA distribution in brain regions was heterogeneous although the concentrations in regions with the highest (hypothalamus) and the lowest (medulla-pons) levels differed less than four-fold. There was no significant correlation between the regional distributions of p-MIAA with those of histamine or its metabolites. pros-Methylhistidine (1 g/kg, i.p.) produced a 20-fold increase in mean levels of p-MIAA and up to a 50-fold increase in levels of pros-methylhistamine (p-MH), a putative intermediate; levels of histamine and its metabolites were unaltered. L-Histidine (1 g/kg, i.p.) or alpha-fluoromethylhistidine (100 mg/kg, i.p.), the irreversible inhibitor of histamine synthesis, did not alter the levels of p-MIAA in brain. Like the levels of t-MIAA, the levels of p-MIAA were unaltered after probenecid administration. Contrary to its effects in lowering t-MIAA levels, pargyline (75 mg/kg, i.p.) produced a slight rise in levels of p-MIAA in all regions. These findings suggest that, in brain, the metabolic pathways of histamine are independent of pathways that generate p-MIAA. Further, since brain is capable of p-MH formation, its use as an internal standard in analytical methods merits caution.

Brain histamine: plasma corticosterone spontaneous locomotor activity and temperature.

Hypothalamic histamine exhibited circadian fluctuations in male Sprague-Dawley rats; low values were found during the dark period when spontaneous locomotor activity (S.L.A.) and temperature were elevated. A relatively high hypothalamic histamine level was observed during the early period of the light cycle and was associated with decreased S.L.A. and temperature. Histamine concentration was high when corticosterone levels were low at the end of the dark cycle and during the morning hours (4 a.m.-1 p.m.); but histamine levels were relatively constant while corticosterone concentration dropped during afternoon and early night hours (4 p.m.-10 p.m.). Furthermore, the lowest hypothalamic histamine level (at 1 a.m.) was associated with the average plasma corticosterone value, thus no consistent relationship between histamine and corticosterone levels could be observed. Circadian fluctuations in brain histamine may support its role in brain function.