title: HA autoreceptor assay with superfused slices of rat brain cortex and electrical stimulation.
abstract: Slices of rat brain cortex previously loaded with [3H]histamine ([3H]HA) via de novo synthesis from [3H]histidine released tritiated histamine ([3H]HA) Ca2+ dependently in a superfused system. Both electrical field stimulation and high levels of K+ ions elicited this release. The extent of release depended on stimulation intensity. Rather strong stimuli, either by high frequency or longer stimulation, were required to elicit sufficient HA release for proper assessment of the concentration-dependence of release inhibition by drugs. The system showed marked depletion (less response per pulse) upon long-continued or successive stimulations. HA added to the superfusion medium inhibited the release evoked by stimulation at frequencies up to 10 Hz or with 30 mM K+ but not the release at higher frequencies or with 45 mM K+. The inhibition was mediated by H3 receptors, was concentration-dependent (pD2 = 7.4) and was complete at 10(-6) M. The H2 agonist impromidine antagonized the inhibition competitively (pA2 = 7.1). It is concluded that this assay in a superfusion system with electrical stimulation is suitable for the assessment of H3 receptor activity of drugs.
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000502:physiology; D004558:Electric Stimulation; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006639:Histidine / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D017446:Impromidine; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011968:Receptors, Histamine / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D006635:Histamine H2 Antagonists; D007093:Imidazoles; D011968:Receptors, Histamine; D006639:Histidine; D017446:Impromidine; D002118:Calcium