Contribution of the histaminergic receptor subtypes to histamine-induced cerebellar granular neurotoxicity.

In the present study, we investigated the effects of histamine and its specific H(1), H(2) and H(3) receptor blockers in cerebellar granular cell culture derived from rat pups. Histamine was applied at 10(-9),10(-8), 10(-7),10(-6), and 10(-5) M for 16 h into the cultures and the highest dose was found to be the most toxic one. Pheniramine (H(1) receptor blocker), ranitidine (H(2) receptor blocker) and thioperamide (H(3) receptor blocker) were applied at 10(-8), 10(-7), 10(-6), 10(-5) M into the flasks prior to histamine in the second step of the experiments. Also, the effect of all of the blockers together at 10(-5) M concentrations was tested on the toxicity induced by 10(-5) M histamine. The H(3) receptor blocker, thioperamide (10(-6) M) was demonstrated to be most effective histamine toxicity blocker. Histamine H(2) blocker, ranitidine, was found to attenuate histamine neurotoxicity at all doses tested, its most effective dose being the highest dose. On the other hand, H(1) blocker, pheniramine, was able to reverse the effect of histamine at 10(-6) and 10(-5) M, but it was found ineffective when given at 10(-9) and 10(-8) M. Combined application of H(1), H(2), and H(3) receptor blockers at 10(-5) M concentrations, 45 min before histamine addition into the flasks at 10(-5) M, was able to reduce cell death score but it was not as effective as H(3) blocker, thioperamide.