Inhibition of hormonally induced inositol trisphosphate production in transfected GH(4)C(1) cells: A novel role for the D-5 subtype of the dopamine receptor
Bh. White et al., Inhibition of hormonally induced inositol trisphosphate production in transfected GH(4)C(1) cells: A novel role for the D-5 subtype of the dopamine receptor, NEUROENDOCR, 69(3), 1999, pp. 209-216
We have previously found that the D-5 dopamine receptor couples to a G-prot
ein other than G(s)alpha, and could be involved in signaling pathways other
than regulation of adenylyl cyclase. To describe interactions of the D-5 r
eceptor with cellular effecters, we used GH(4)C(1) cells transfected with c
DNA for the human Dg receptor. Thyrotropin-releasing hormone (TRH, 100 nM)
stimulated accumulation of inositol phosphates (IPs) fivefold in D(5)GH(4)C
(1) cells. Dopamine (DA, 10 mu M) inhibited TRH-stimulated IP values by 29%
; at higher concentrations (100 mu M), maximal inhibition of 61% was observ
ed. The D-5 agonist SKF R-38393 (10 mu M) mimicked this effect (28% inhibit
ion). SCH 23390, a D-5 antagonist, blocked the inhibition caused by both DA
and SKF R-38393, Spiperone, a D-2 receptor antagonist, did not block the i
nhibition. The D-2 agonist (+/-)-2-(N-phenylethyl-N-propyl)amino-5-hydroxyt
etralin (PPHT) did not inhibit TRH-stimulated IP production, nor did it aug
ment the effect of D-5 agonists. The DA-mediated suppression of IP levels w
as not sensitive to pertussis toxin; cholera toxin blocked both TRH stimula
tion and DA suppression of IP accumulation in response to 100 nM TRH. Neith
er dibutyryl cAMP nor forskolin lowered IP formation in response to TRH. Ph
orbol ester decreased TRH-stimulated IP accumulation in D(5)GH(4)C(1) cells
; however, an inhibitor of protein kinase C (PKC) did not block the effect
of DA.