Effect of neurotransmitters on the in vitro release of immunoreactive thyrotropin-releasing hormone from rat mediobasal hypothalamus.

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 H2 receptors; conversely, the response to histamine was blocked by the addition of a H2 (metiamide; 10(-6) M) but not of a H1 (mepyramine; 10(-6) M) antagonist to the incubation medium. Dopamine (10(-7) M) slightly inhibited the release of TRH, but antagonists of dopamine receptors (10(-7)-10(-6) M fluphenazine or 10(-6) M alpha-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 gamma-aminobutyric acid and acetylcholine (tested at concentration of 10(-7) M) did not alter the basal release of the tripeptide.