scholarly journals Importance of thiol groups in ligand binding to D2 dopamine receptors from brain and anterior pituitary gland

1992 ◽  
Vol 281 (2) ◽  
pp. 377-380 ◽  
Author(s):  
P L Chazot ◽  
P G Strange

The effects of the thiol group reagent 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) on D2 dopamine receptors have been examined in three brain regions (caudate nucleus, putamen and olfactory tubercle), and in the anterior and neurointermediate lobes of the pituitary gland. Whereas the receptors in brain were insensitive to DTNB, a dose-dependent inhibition of [3H]spiperone binding to D2 receptors in both lobes of the pituitary gland was observed. The effects in the pituitary could be reversed by subsequent treatment with dithiothreitol and could be prevented by prior occupancy of the receptor binding site with a ligand. The effect of DTNB was to decrease the number of ligand-binding sites without altering the affinity of those remaining. The results show that modification of a thiol group of the D2 dopamine receptor in the two lobes of the pituitary gland tested here significantly affects ligand binding. There is therefore a difference between the D2 dopamine receptor populations in brain and pituitary in their sensitivity to modification by DTNB, and this may imply the existence of different receptor isoforms in the two issues.

1986 ◽  
Vol 238 (3) ◽  
pp. 817-823 ◽  
Author(s):  
W M Abbott ◽  
P G Strange

Five stable hybridomas have been obtained that secrete monoclonal antibodies against the D2-dopamine receptor-selective drug spiperone. Each monoclonal antibody has been characterized in terms of its ability to bind a range of dopamine-receptor-selective ligands. One monoclonal antibody has been purified by Protein A affinity chromatography and used to immunize mice. Anti-idiotypic antisera and one hybridoma secreting an anti-idiotypic monoclonal antibody were obtained and shown to inhibit [3H]spiperone binding to the anti-spiperone antibody used for immunization. Neither the antisera nor the anti-idiotypic monoclonal antibody, however, inhibited binding of [3H]spiperone to D2-dopamine receptors.


Author(s):  
H.A. Robertson

ABSTRACT:The addition of a D2 agonist such as bromocriptine to L-Dopa therapy can often improve the response of patients with Parkinson’s disease dramatically. Simultaneous activation of D1 and D2 dopamine receptors can produce a synergistic effect on locomotion in rats and primates. However, despite the importance of this addition of a D2 agonist to the D1/D2 agonist L-Dopa, little is known of the sites of action of these agents. Recent work suggests that, in addition to D1 and D2 dopamine receptor sites in the striatum (caudate-putamen), L-Dopa and D1 agonists have important effects at D1 dopamine receptors in the substantia nigra. Animal experiments suggest that D1 and D2 dopamine receptor agonists probably also affect different outflow pathways from the striatum. An understanding of these pathways and how dopamine agonists affect them gives insight into some of the clinical problems experienced in treating Parkinson’s disease (the “on-off phenomenon, for example). D1/D2 dopamine receptors also differentially affect gene expression and regulation in the striatum. An understanding of the anatomical and biochemical location of the actions of dopamine receptor agonists will be important in maximizing the beneficial effects and minimizing the side-effects of both presently-used drugs and new treatments.


1987 ◽  
Vol 413 (2) ◽  
pp. 205-212 ◽  
Author(s):  
Johan F. Plantjé ◽  
Jacques Schipper ◽  
Piet F.H.M. Verheijden ◽  
Johannes C. Stoof

Biochemistry ◽  
1995 ◽  
Vol 34 (41) ◽  
pp. 13635-13641 ◽  
Author(s):  
Ursula M. D'Souza ◽  
Philip G. Strange

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