Regulation of heterogeneity in D2 dopamine receptor gene expression among individual melanotropes in the rat pituitary intermediate lobe.
The regulation of D2 dopamine receptor binding, immunoreactivity, and mRNA was studied in melanotropes of the intermediate lobe of the rat pituitary. D2 dopamine receptor-binding experiments showed that chronic haloperidol treatment (2 mg/kg for 14 days) significantly increased the Bmax but not Kd of [3H]spiperone binding, whereas bromocriptine treatment (2 mg/kg for 14 days) produced no change in either parameter. Immunohistochemical experiments revealed that all melanotropes contained D2 receptor immunoreactivity but the D2long receptor isoform was intensely expressed by comparatively few melanotropes scattered among cells that contained substantially lower staining intensities. Chronic haloperidol treatment increased the overall intensity of total D2 receptor staining and concurrently increased both the number and staining intensity of melanotropes immunoreactive for the D2long isoform. Bromocriptine treatment produced no change in overall staining intensity; however, the number of melanotropes staining for the D2long isoform increased significantly. Nonradioactive in situ hybridization histochemistry further revealed that individual melanotropes contained differing amounts of both total D2 receptor and D2long mRNAs; the heterogeneity in D2long receptor expression was particularly striking. Following haloperidol treatment, D2 receptor mRNA levels increased in all melanotropes. Following bromocriptine treatment most melanotropes contained very low levels although many melanotropes retained substantial amounts of D2 receptor mRNA. The parallel increase in D2 receptor-binding densities, immunoreactivity, and mRNA levels following chronic antagonist treatment emulates the classic paradigm by which a cell increases its receptor population. Chronic agonist treatment did not follow the inverse paradigm and revealed heterogeneous regulation of a discrete subpopulation of melanotropes.
Chronwall
B M
BM
School of Biological Sciences, University of Missouri, Kansas City 64108.
Dickerson
D S
DS
Huerter
B S
BS
Sibley
D R
DR
Millington
W R
WR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001971:Bromocriptine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D017403:In Situ Hybridization; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000096:biosynthesis / Q000235:genetics*
D011954:Receptors, Dopamine; D001971:Bromocriptine; D011333:Pro-Opiomelanocortin; D006220:Haloperidol