Evidence that LY-141865 specifically stimulates the D-2 dopamine receptor
Abstract
Available evidence suggests the existence of multiple categories of dopamine receptor1-4. According to the classification scheme used here5, dopamine receptors can be divided into two general categories, D-l and D-2. The dopamine receptors in the bovine parathyroid gland6-8 and carp retina9,10 exemplify the former category, and the dopamine receptors on the mammotrophs11,12 and melanotrophs13,14 of the pituitary gland exemplify the latter. Stimulation of a D-1 receptor enhances the formation of cyclic AMP, whereas stimulation of a D-2 receptor does not4,5. The availability of dopaminergic agonists which specifically activate either a D-1 or a D-2 receptor would facilitate pharmacological investigation of the physiological responses to dopamine; however, to date, an agonist specific for the D-2 receptor has not been available. Dopamine and other catecholamines stimulate both types of receptor6-14 ergolines (such as lergotrile and lisuride) stimulate the D-2 receptor13-15 but antagonize the D-1 receptor8,16-18 some agonists acting on the D-2 receptor (such as apomorphine) both stimulate and block the D-1 receptor6,8. Although one report claims that S-584 may selectively stimulate the dopamine receptor on mammotrophs19, according to another, S-584 stimulates the striatal dopamine-sensitive adenylate cyclase20. Several recently synthesized compounds containing various portions of the ergoline ring system stimulate the D-2 receptor on mammotrophs21. We report here that one of these ergoline analogues, LY-141865 or `38, R = pro'21, stimulates the D-2 receptor in the intermediate lobe (IL) of the rat pituitary gland but does not interact with the D-1 receptor in carp retina.
- Publication:
-
Nature
- Pub Date:
- July 1981
- DOI:
- 10.1038/292463a0
- Bibcode:
- 1981Natur.292..463T