Effect of dopamine on adenylate cyclase activity, polyphosphoinositide metabolism and cytosolic calcium concentrations in frog pituitary melanotrophs.
It has previously been shown that dopamine plays a pivotal role in the regulation of alpha-melanocyte-stimulating hormone (alpha-MSH) secretion from the intermediate lobe of the pituitary. In the present study, we have investigated the various intracellular mechanisms that are associated with the action of dopamine on frog pituitary melanotrophs. Dopamine reduced forskolin-stimulated cyclic adenosine monophosphate (cAMP) production and the inhibitory effect of dopamine was blocked by the dopaminergic D2 receptor antagonist sulpiride. The D2 receptor agonist apomorphine inhibited incorporation of [3H]inositol into membrane phospholipids. Dopamine also inhibited the formation of inositol trisphosphate and provoked accumulation of phosphatidylinositol bisphosphate. The inhibitory effect of dopamine on inositol trisphosphate production was mimicked by D2 receptor agonists and blocked by sulpiride. Using a double-wavelength microfluorimetric approach, we found that dopamine caused a rapid and transient decrease in K(+)-evoked stimulation of intracellular calcium concentration. The time-courses of the responses of the various intracellular messengers indicate that blockage of voltage-dependent calcium channels is the primary event associated with activation of dopamine D2 receptors, while inhibition of polyphosphoinositide breakdown, related to blockage of voltage-dependent calcium channels, and reduction of cAMP production are secondary events which may contribute to the sustained inhibitory effect of dopamine on alpha-MSH release.
European Institute for Peptide Research, CNRS URA 650, UA INSERM, University of Rouen, Mont-Saint-Aignan, France.
L
L
Desrues
M
M
Lamacz
B G
BG
Jenks
H
H
Vaudry
M C
MC
Tonon
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D003600:Cytosol / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011895:Rana ridibunda; D013469:Sulpiride / Q000494:pharmacology; D000521:alpha-MSH / Q000378:metabolism*
D015220:Calcium Channels; D010716:Phosphatidylinositols; D005576:Colforsin; D000521:alpha-MSH; D013469:Sulpiride; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium; D004298:Dopamine