INVITRO RELEASE OF HYPOTHALAMIC BETA-ENDORPHIN (BETA-E) BY ARGININE VASOPRESSIN, CORTICOTROPIN-RELEASING HORMONE AND 5-HYDROXYTRYPTAMINE - EVIDENCE FOR RELEASE OF OPIOID ACTIVE AND INACTIVE BETA-E FORMS

The aims of the present experiments were: 1) to test whether substances which modulate beta-endorphin-immunoreactive βE-ir release from the pituitary gland might act similarly in hypothalamic tissue; and 2) to further characterize the βE-ir forms which are released from hypothalamus. To address these questions, hypothalamic tissue was incubated in vitro for 10 min periods in either normal media (basal conditions) or in media containing 55 mM KCl or one of several other test substances (stimulation conditions) and release was estimated by measuring the βE-ir concentrations in the media. Depolarizing concentrations of K+ increased βE-ir release 2-3 fold over basal levels and this effect appeared to be Ca2+-dependent. Dose-dependent increases in βE-ir release were elicited by nanonolar to micromolar concentrations of either corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), or 5-hydroxytryptamine (5-HT). Conversely, dopamine (1 μM) inhibited both the basal and K+-stimulated release of βE-ir from hypothalamus. Gel filtration chromatography revealed that βE1-31 and βE1-27 βE1-26 were the primary βE-ir peptides released under either basal or CRH-stimulated conditions; the relative amounts of the βE-ir peptides found in the media were nearly identical to those found in the hypothalamus itself. This result indicates that the release of different βE-ir peptides into the media appears to be proportional to the relative amounts stored in tissue. In light of the critical roles of CRH and AVP in mediating stress responses in the anterior pituitary, the data showing that the same neurohormones/transmitters (i.e., CRH, AVP, 5-HT, and DA) modulate βE-ir release in both the pituitary gland and the hypothalamus suggests that endocrine and central POMC systems involved in stress responses might be regulated in a coordinate manner. © 1990.