Effect of Neurotransmitters on the in Vitro Release of Immunoreactive Thyrotropin-Releasing Hormone from Rat Mediobasal Hypothalamus*

Abstract

The in vitro release of TRH from hypothalamic fragments or purified nerve endings (synaptosomes) has been evaluated after incubation for 10 min in the presence of various concentrations of K⁺ or neurotransmitters. Release of the hormone from fragments but not from synaptosomes was enhanced in the presence of 56 mM K₊ in a Ca⁺⁺-dependent manner. Neurotransmitter effects were thus tested on the fragments. Addition of histamine (10^-7-10^-5 M) induced a significant increase over the basal release of TRH. A comparable effect was obtained with dimaprit (10^-5 M), a highly specific agonist of histamine H₁ receptors; conversely, the response to histamine was blocked by the addition of a H₁ (metiamide; 10^-6 M) but not of a H₁ (mepyramine; 10^-6 M) antagonist to the incubation medium. Dopamine (1O^-7 M) slightly inhibited the release of TRH, but antagonists of dopamine receptors (10^-7–10^-6 M fluphenazine or 10^-6 M α-flupentixol) exhibited an inhibitory effect by themselves, so that specific receptors involved in mediating dopamine actions could not be further characterized. In contrast, noradrenalin, serotonin, γ-aminobutyric acid, and acetylcholine (tested at concentrations of 10^-7 M) did not alter the basal release of the tripeptide