Autoinhibition of histamine release by H3 receptors in rat brain cortex depends on stimulation frequency.
Rat cortical slices preloaded with [3H]histidine released [3H]histamine upon electrical stimulation or after depolarization with elevated K+ levels. The release was dependent on the presence of Ca2+, suggesting a neurosecretory process. Histamine has been shown to inhibit its own release mediated by an autoreceptor belonging to the H3-receptor subclass. In this study we have investigated the autoinhibition using different electrical field stimulation conditions (1, 10, 20 and 33.3 Hz). Applying electrical stimulation, the inhibition of [3H]histamine release by histamine is decreased when the stimulation frequency is elevated. When stimulated with 1 Hz histamine is able to block [3H]histamine release completely, with a p(EC50) of 8.1 +/- 0.1. At higher frequencies histamine still blocks [3H]histamine release completely, but with a lower p(EC50).
Vrije Universiteit, Faculty of Chemistry, Department of Pharmacochemistry, Amsterdam, The Netherlands.
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van der Vliet
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Bast
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Timmerman
D000818:Animals; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000502:physiology; D004558:Electric Stimulation; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011968:Receptors, Histamine / Q000378:metabolism*; D018100:Receptors, Histamine H3
D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D011188:Potassium; D002118:Calcium