Differential coupling with pertussis toxin-sensitive G proteins of dopamine and somatostatin receptors involved in regulation of adenohypophyseal secretion.
D2 dopamine receptors and somatostatin receptors in adenohypophyseal cells are coupled through G proteins to various transduction mechanisms. To study the involvement of these different transduction mechanisms and of various G proteins in the dopamine and somatostatin regulation of prolactin (PRL), growth hormone (GH) and thyroid-stimulating hormone (TSH) secretions, we have pretreated the adenohypophyseal cells in primary culture with increasing doses of pertussis toxin. The guanosine triphosphate (GTP) dependency of the negative coupling of dopamine and somatostatin receptors with adenylate cyclase in the same membrane preparation from anterior pituitary cells was different. In fact, higher GTP doses were requested to obtain dopamine inhibition, suggesting that different G proteins were involved in the coupling of these two receptors with adenylate cyclase. However, the inhibition of adenylate cyclase activity by both neurohormones was fully sensitive to pertussis toxin pretreatment with a similar IC50 for the toxin. The IC50 for the toxin was also similar for the blockade of dopamine or somatostatin inhibition of the three-hormone secretion as well as for the stimulation on basal PRL or GH secretion or the reduction of thyrotropin-releasing hormone (TRH)-stimulated prolactin secretion, suggesting that the toxin acts through similar mechanisms on these different phenomena. Pretreatment of the cells with Bordetella pertussis toxin differentially affected the effects of both neurohormones on the three cell types. A complete reversion of the inhibition of secretion was observed only in the case of somatostatin on PRL and TSH cells. In contrast, the somatostatin inhibition of GH secretion was only partially reversed by the pertussis toxin pretreatment. This was also the case of dopamine inhibition of PRL secretion. It can be concluded that: (1) On PRL secretion dopamine and somatostatin do not share all the mechanisms since the intensity of their inhibition and the reversibility of their effects by pertussis toxin were differential. (2) Different mechanisms of action are implicated in the effect of somatostatin on PRL, GH and TSH secretions. (3) Different G proteins might be involved in the coupling of dopamine and somatostatin receptors with adenylate cyclase.
Musset
F
F
U. 159 INSERM, Paris, France.
Bertrand
P
P
Kordon
C
C
Enjalbert
A
A
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000145:classification / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism; D037342:Pertussis Toxin; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D017481:Receptors, Somatostatin; D015290:Second Messenger Systems / Q000187:drug effects*; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000494:pharmacology; D013972:Thyrotropin / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D011954:Receptors, Dopamine; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D004298:Dopamine