Thyrotropin-releasing hormone and histidyl-proline diketopiperazine: stimulation of secretion from hypothalamic fragments in vitro by depolarizing agents.
The influence of depolarizing agents on the release of TRH and histidyl-proline diketopiperazine [C(HP)] from rat hypothalami was examined in vitro. Thin hypothalamic fragments from two separate animals were incubated in Krebs-Ringer bicarbonate media. Immunoreactive TRH and C(HP) released into medium were determined by specific RIAs. Potassium and ouabain, a Na+/K+-ATPase inhibitor, stimulated TRH and C(HP) secretion in a graded fashion, but the magnitudes of C(HP) secretory responses were less than those of TRH. The stimulation by KCl and ouabain was inhibited by the addition of verapamil, a Ca2+ channel blocker, or omission of Ca2+ from medium in the presence of EGTA. Veratridine, a Na+ channel activator, also stimulated TRH and C(HP) release from rat hypothalami, and this stimulation was completely blocked by tetrodotoxin, a Na+ channel blocker. The results of this study indicate that TRH and C(HP) release from rat hypothalami are stimulated by membrane depolarization in vitro and depend on Na+ and Ca2+ influx.
D000818:Animals; D004533:Egtazic Acid / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000378:metabolism*; D010879:Piperazines / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D010456:Peptides, Cyclic; D010879:Piperazines; D013779:Tetrodotoxin; D004533:Egtazic Acid; D010042:Ouabain; D013973:Thyrotropin-Releasing Hormone; D011189:Potassium Chloride; D014701:Veratridine; D014700:Verapamil; C015924:histidyl-proline diketopiperazine