Dopaminergic Mediation of the Effect of Elevated Potassium on the Release of Pro-Opiomelanocortin-Derived Peptides from the Pars intermedia of the Rat Pituitary

Publisher Website
Google Scholar
Abstract
The pars intermedia (PI) of the adenohypophysis synthesizes pro-opiomelanocortin (POMC), which through post-translational processing, gives rise to a group of chemically related peptides, including αMSH, ACTH, CLIP, LPHs and endorphins. We investigated the control of release of these peptides using an in vitro system. We perifused either acutely dispersed rat PI cells or intact rat neurointermediate lobes (NI). Perifusion medium was subjected to a series of bioassays (BA) and radioimmunoassays (RIA) (including MSH-BA, ACTH-BA, ACTH-RIA, αMSH-RIA, LPH-RIA) and a receptor-binding assay for morphine-like activity. Both dispersed PI cells and intact NI responded to dopamine (DA) with a dose-related and sustained decrease in release of all of the assayable peptides. The response to an 8-fold elevation in K+ in the medium (8K) differed in the dispersed PI cells and intact NI. Whereas the PI cells responded with a transient ‘spike’ of release of all of the assayable peptides, the NI responded to 8K with a sustained decrease in release of all of the assayable peptides, except for ACTH-BA. To explain this difference in response, we tested the hypothesis that in dispersed PI, 8K acts directly on the parenchymal cells to elicit a transient release of peptides, while in intact NI, 8K acts preferentially on the dopaminergic neurones in the gland to release DA. This endogenous DA then acts directly on the PI cells to inhibit release of peptides. The DA-antagonist, d-butaclamol (dBUT, 10–7–10–5M) was used to test this hypothesis. dBUT abolished the DA-induced inhibition of peptide release, and converted the inhibitory response to 8K of intact NI to the transient ‘spike’ response typical of dispersed PI cells. These results strongly support the participation of the dopaminergic arcuato-hypophyseal system in inhibitory control of the release of POMC-derived peptides from the PI.