Monoamine release by compound 48/80 from nonmast cell compartments in mouse brain slices.
In the present study we investigated the specificity of the releasing effects of compound 48/80 (48/80) for mast cell vs. neuronal histamine (HA) from hypothalamic slices. In addition, we investigated the selectivity of the releasing effects of 48/80 for HA compared to other neurotransmitters. Brain slices from W/W mice, a genetic mutant devoid of mast cells, and +/+ mice, its normal counterpart, were used. Hypothalamic slices were labeled with [3H]HA or [3H]histidine. 48/80 elicited similar degrees of release of [3H]HA from both mouse strains, irrespective of the label used. In addition, 48/80 produced marked increases in the efflux of dopamine (DA), serotonin (5-HT), norepinephrine (NE) and modest increases in the efflux of acetylcholine (ACh). These effects were concentration-dependent and the magnitude of release varied with the transmitter examined (DA greater than NE greater than 5-HT much greater than ACh = HA). Transmitter efflux induced by 48/80 was not altered by low calcium concentrations or by tetraethylammonium; whereas, release evoked by electrical stimulation was reduced and increased, respectively, by these treatments. In mouse striatal slices preloaded with [3H]DA, 48/80 induced an initial increase in [3H]DA efflux, followed by a marked increase in the efflux of its metabolite, [3H]-3,4-dihydroxyphenylacetic acid. Nomifensine failed to inhibit, whereas reserpine pretreatment reduced 48/80-induced efflux of 3H. In summary, these results indicate that the incubation of hypothalamic slices with [3H]HA or [3H]histidine labels HA neurons selectively and that 48/80 (10-100 micrograms/ml) releases HA from nonmast cell compartments.(ABSTRACT TRUNCATED AT 250 WORDS)
Lovenberg
T W
TW
Department of Pharmacology, University of North Carolina, Chapel Hill.
Cubeddu
L X
LX
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation; D006636:Histamine Release; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D012110:Reserpine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D004298:Dopamine; D009638:Norepinephrine