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An hypothesis of the molecular structure of the dopamine receptor.

Authors
  • Smythies, J R
Type
Published Article
Journal
Medical Hypotheses
Publisher
Elsevier
Publication Date
Dec 01, 1981
Volume
7
Issue
12
Pages
1449–1456
Identifiers
PMID: 7334949
Source
Medline
License
Unknown

Abstract

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.

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