Lack of coupling of D-2 receptors to adenylate cyclase in GH-3 cells exposed to epidermal growth factor. Possible role of a differential expression of Gi protein subtypes.
Exposure of GH-3 cells to epidermal growth factor for 4 consecutive days induced the expression of both D-2(415) and D-2(444) dopamine-receptor isoforms. Epidermal growth factor also promoted a remarkable increase in the content of Gi3 protein, which is responsible for receptor-induced activation of potassium channels in GH-3 cells. D-2 receptors in this model apparently activate a specific transducing pathway, leading to opening of potassium channels and inhibition of prolactin release by cAMP-independent mechanisms. This is shown by: 1) the selective D-2 agonist quinpirole, while inactive on vasoactive intestinal peptide-induced prolactin release, strongly inhibited the hormone secretion induced by neurotensin; 2) quinpirole, up to 100 microM, did not inhibit cAMP production evoked by vasoactive intestinal peptide both in intact cells and in broken cell membrane preparations; and 3) quinpirole and other D-2 agonists strongly potentiated Rb+ efflux when measured in a nominally calcium-free reaction solution containing 100 mM potassium (voltage-dependent component), but did not modify Rb+ efflux if measured in a reaction solution containing 1 mM calcium and 5 mM potassium (calcium-activated, cAMP-dependent component).
Institute of Pharmacology and Experimental Therapeutics, School of Medicine, University of Brescia, Italy.
C
C
Missale
F
F
Boroni
L
L
Castelletti
R
R
Dal Toso
N
N
Gabellini
S
S
Sigala
P
P
Spano
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D004815:Epidermal Growth Factor / Q000502:physiology*; D004873:Ergolines / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D019257:Quinpirole; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D012413:Rubidium / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D015221:Potassium Channels; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D005576:Colforsin; D019257:Quinpirole; D014660:Vasoactive Intestinal Peptide; D009496:Neurotensin; D004815:Epidermal Growth Factor; D011388:Prolactin; D004247:DNA; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D012413:Rubidium; D004298:Dopamine