Inhibition of alpha-MSH secretion is associated with increased cyclic-AMP egress from the neurointermediate lobe of Xenopus laevis.
Cyclic-AMP is known to be released from cells and tissues and the amounts released have been reported to reflect intracellular cAMP levels. To measure cAMP release the phosphodiesterase inhibitor IBMX is often used to increase the amount of cAMP to a detectable level. Using this method to follow cAMP dynamics of melanotrope cells in the neurointermediate pituitary lobe of the amphibian Xenopus laevis we show that the alpha-MSH secreto-inhibitors baclofen (GABAB receptor agonist) and dopamine inhibit cAMP release, confirming the idea that these factors inhibit alpha-MSH secretion by reducing adenylyl cyclase activity. Using a sensitive cAMP radioimmunoassay we were able to measure cAMP release from Xenopus neurointermediate lobes in the absence of IBMX. Both baclofen and dopamine appeared to inhibit alpha-MSH secretion but strongly stimulated the release of cAMP. This indicates that the extracellular cAMP level is not a reliable parameter to measure the intracellular cAMP level in the absence of IBMX. The data furthermore suggest that cAMP release is a physiologically regulated process, which might be involved in lowering intracellular cAMP levels associated with a cellular secretory compartment. No apparent differences could be found in the lobe content of cAMP at the termination of secreto-inhibitor treatment, leading to the idea that the cAMP compartment associated with secretion in small relative to the total amount of cAMP present in the lobe.
Leenders
H J
HJ
Department of Cellular Animal Physiology, Nijmegen Institute for Neurosciences, University of Nijmegen, The Netherlands.
Jenks
B G
BG
Roubos
E W
EW
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D014982:Xenopus laevis / Q000378:metabolism*; D000521:alpha-MSH / Q000037:antagonists & inhibitors* / Q000378:metabolism
D018755:GABA Agonists; D010726:Phosphodiesterase Inhibitors; D000521:alpha-MSH; D000242:Cyclic AMP; D001418:Baclofen; D015056:1-Methyl-3-isobutylxanthine; D004298:Dopamine