An hypothesis of the molecular structure of the dopamine receptor.
Neurotensin has psychopharmacological properties similar to dopamine receptor blocking drugs. A Chou and Fasman analysis of the primary sequence suggests that the sequence 1-6 forms an alpha-helix broken by pro (7) and 9-12 forms a beta-turn. This allows the peptide molecule to form an amphoteric structure with, on one side, the evenly space array - p glu - glu - arg - arg - ( delta- - + +) which is self-complementary. Thus, two molecules of neurotensin placed head to tail can form a Kusnetsov-Ghokov grid with four cross-links (p glu and glu to arg - arg) x 2. The walls of a shadow potential receptor cup are formed by asn(5), pro(7), ile(12) and pro(10) on each side. CPK model building experiments indicate that this structure is complementary to a wide range of dopamine agonists and antagonists. Therefore, the hypothesis is presented that neurotensin may mimic part of the DA receptor protein. Thus it may form a 'false' receptor and trap dopamine molecules, thus diminishing the dopamine effect. Similarities between this proposed structure and a model of the molecular structure of the acetylcholine receptor are detailed.
D001058:Apomorphine / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004298:Dopamine / Q000378:metabolism; D009496:Neurotensin; D010868:Pimozide / Q000378:metabolism; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013881:Thioridazine / Q000378:metabolism
D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D010868:Pimozide; D009496:Neurotensin; D013134:Spiperone; D001058:Apomorphine; D013881:Thioridazine; D004298:Dopamine