Evidence that LY-141865 specifically stimulates the D-2 dopamine receptor

• Published in: Nature (London) 1981-07, Vol.292 (5822), p.463-465
• Main Authors: Tsuruta, K, Frey, E. A, Grewe, C. W, Cote, T. E, Eskay, R. L, Kebabian, J. W
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - metabolism; Animals; Apomorphine - pharmacology; Cholera Toxin - pharmacology; Ergolines - pharmacology; Humanities and Social Sciences; letter; Melanocyte-Stimulating Hormones - metabolism; multidisciplinary; Pituitary Gland - drug effects; Quinpirole; Rats; Receptors, Dopamine - drug effects; Retina - drug effects; Science; Science (multidisciplinary); Secretory Rate - drug effects
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/292463a0

Available evidence suggests the existence of multiple categories of dopamine receptor 1–4 . According to the classification scheme used here 5 , dopamine receptors can be divided into two general categories, D-l and D-2. The dopamine receptors in the bovine parathyroid gland 6–8 and carp retina 9,10 exemplify the former category, and the dopamine receptors on the mammotrophs 11,12 and melanotrophs 13,14 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 not 4,5 . 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 receptor 6–14 ; ergolines (such as lergotrile and lisuride) stimulate the D-2 receptor 13–15 but antagonize the D-1 receptor 8,16–18 ; some agonists acting on the D-2 receptor (such as apomorphine) both stimulate and block the D-1 receptor 6,8 . Although one report claims that S-584 may selectively stimulate the dopamine receptor on mammotrophs 19 , according to another, S-584 stimulates the striatal dopamine-sensitive adenylate cyclase 20 . Several recently synthesized compounds containing various portions of the ergoline ring system stimulate the D-2 receptor on mammotrophs 21 . 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.