&lt;i&gt;In vitro&lt;/i&gt; Release of ACTH from Dispersed Rat Pars Intermedia Cells. II. Effect of Neurotransmitter Substances

We used an in vivo pharmacological approach to investigate the potential influence of serotonin (5-HT) on peptide release from the intermediate lobe (IL) of the rat pituitary. Plasma levels of α-melanocyte-stimulating hormone (α-MSH) as well as the ultrastructural appearance of IL cells were used as indicators of IL secretory activity. Plasma β-endorphin levels were also measured to assess the effectiveness of 5-HT-acting drugs. Intraperitoneal administration of 5-hydroxy-L-tryptophan, the synthetic precursor of 5-HT, dramatically elevated the content of 5-HT in the neurointermediate lobe but did not alter plasma titers of α-MSH. Treatment with the 5-HT reuptake blocker fluoxetine elevated plasma levels of β-endorphin but not α-MSH. Administration of the 5-HT₁/5-HT₂ agonist MK-212 produced an elevation in both plasma α-MSH and β-endorphin levels. Quantitative morphometry of IL cells at the ultrastructural level revealed that MK-212 treatment selectively causes depletion of electron-lucent but not electron-dense secretory granules from the cytoplasm of IL cells. Pretreatment with the selective D₂ dopamine agonist apomoφhine blocked MK-212-induced release of α-MSH but not β-endorphin. Our results show that manipulation of 5-HT synthesis/reuptake does not affect release of α-MSH, but that direct activation of 5-HT receptors with the nonselective agonist MK-212 stimulates α-MSH release. The ability of apomoφhine to block MK-212-induced release of α-MSH suggests a direct antagonism between dopaminergic and serotonergic regulation of α-MSH release.

Section: Discussionsupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

In vivo Effects of Serotonergic Agents on AIpha-MeIanocyte-StimuIating Hormone Secretion

Carr¹,

Saland²,

Samora³

et al. 1991

“…The mean basal concentration (weight and molar basis) of active peptide released from NI was calculated near the beginning (fractions [14][15][16][17][18][19][20][21] and at the end (last 4 fractions) The peptides listed were tested in the assays at 5-6 concentrations to determine relative potencies and parallelism of slopes of dose-re sponse curves. Values are given as percent of potency of peptide used as standard in each assay, either on weight (top) or molar (bottom) basis.…”

Section: Relative Levels O F Activity Detected By Each Assaymentioning

confidence: 99%

Differential Control of the Release of Pro-Opiomelanocortin-Derived Peptides from the Pars intermedia of the Rat Pituitary

Randle¹,

Moor²,

Kraicer³

1983

The pars intermedia (PI) of the adenohypophysis synthesizes pro-opiomelanocortin, 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 neurointermediate lobes (NI). Perifusion medium and cell extracts were subjected to a series of bioassays (BA) and radioimmunoassays (RIA) (including MSH-BA, αMSH-RIA, ACTH-BA, ACTH-RIA, LPH-RIA) and a receptor-binding assay for morphine-like activity (MLA). The relative amounts of release of the various peptide activities was examined under basal and stimulated conditions. Under basal conditions, intact NI released approximately equal amounts of αMSH immunoactivity, MSH bioactivity and MLA, slightly less ACTH and LPH immunoactivity and far less ACTH bioactivity. Relative to αMSH immunoactivity, the rate of release of ACTH bioactivity decreased in the course of an experiment while the release of the other peptide activities increased. The peptide activities were released from dispersed PI cells in relative amounts similar to those from intact NI. The relative amounts of peptide activities contained in extracts of dispersed PI cells differed from the amounts released such that when compared to αMSH immunoactivity, the release of LPH and ACTH immunoactivities and MLA is 3–4 times greater while the release of ACTH bioactivity is one-half. Serotonin (10^–7–10^–5M) markedly stimulated the release of ACTH bioactivity from both dispersed PI cells and intact NI in a dose-related manner. Serotonin had a smaller stimulatory effect on the release of αMSH and LPH immunoactivity but had no effect on the release of MLA and ACTH immunoactivity. These observations indicate that there is differential control of the release of POMC-derived peptides from the rat PI.

“…neurotransmittors, which could be destroyed in our extracts, might have an effect. Kraicer [1976b] showed that serotonin could stimulate the ACTH release from IL cells.…”

Section: Discussionmentioning

confidence: 99%

In vitroRegulation of ACTH Release from Neurointer mediate Lobe of Rat Hypophysis. I. Effect of Crude Hypothalamic Extracts

Briaud¹,

Koch²,

Lutz-Bucher³

et al. 1978

Using incubated glands, we showed that cerebral cortex and liver extracts (CCE and LE) stimulated ACTH release from neurointermediate lobe (NIL) of hypophysis as well as hypothalamus extract (HE) did. Moreover, the HE-induced ACTH release was much smaller for the NIL (1.9 × basal level) than for the anterior lobe (AL; 13.7 × basal level). Thus, under these conditions, HE seemed to have no specific effect on NIL ACTH release. Using superfused glands, we showed: (a) that both spontaneous and HE-induced ACTH release decreased during superfusion; (b) that using this system, a specific stimulatory effect of HE on NIL was observed. In contrast to HE, CCE and LE had only a small effect on NIL ACTH release (always less than 20% of that caused by HE) which could be considered as a nonspecific response; (c) that trypsin suppressed the stimulating effect of HE as well on NIL as on AL; and (d) that arginine antidiuretic hormone (ADH) was not responsible for the stimulating effect of HE on NIL ACTH release, because synthetic ADH had no effect and HE containing ADH (from normal rats) or HE containing no ADH (from Brattleboro rats or from immunoneutralization of ADH in normal HE) had the same effect. From these results, we can conclude that HE contain a peptidic factor different from ADH which is able to stimulate in vitro release of ACTH from the NIL.