ACTH/MSH-like peptides inhibit the binding of dopaminergic ligands to the dopamine D2 receptor in vitro
| Autor: | Jeroen A.D.M. Tonnaer, Wouter J. Florijn, Thijs de Boer, Jan W. van Nispen, Dirk H.G. Versteeg |
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| Rok vydání: | 1991 |
| Předmět: |
Agonist
Male endocrine system Spiperone medicine.medical_specialty Apomorphine Tetrahydronaphthalenes medicine.drug_class Dopamine Agents Molecular Sequence Data Biology In Vitro Techniques Ligands Receptors Dopamine Structure-Activity Relationship Adrenocorticotropic Hormone Dopamine Internal medicine Dopamine receptor D2 medicine Animals Amino Acid Sequence Melanocyte-Stimulating Hormones Receptor Pharmacology 8-Hydroxy-2-(di-n-propylamino)tetralin Dopaminergic Rats Inbred Strains Receptor antagonist Peptide Fragments Rats Quinuclidinyl Benzilate Kinetics Endocrinology Dopamine receptor Cosyntropin hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | European journal of pharmacology. 207(1) |
| ISSN: | 0014-2999 |
| Popis: | ACTH-(1-24) decreased the binding of the dopamine D 2 receptor agonist, [ 3 H]N-propylnorapomorphine ([ 3 H]NPA), to rat striatal membranes in a concentration-dependent manner, with a K i of 5 × 10 −7 M. Saturation curves for [ 3 H]NPA binding in the presence of increasing concentrations of ACTH-(1-24) were performed. Scatchard analysis in the presence of ACTH-(1-24) revealed an increased dissociation constant (K d ), while the binding capacity (B max ) was not affected by the peptide, suggesting an apparent competitive interaction between ACTH-(1-24) and [ 3 H]NPA. ACTH-(1-24) also reduced the binding of the dopamine D 2 receptor antagonist [ 3 H]spiperone to striatal membranes, with a K i of 10 −6 M. Much higher concentrations of ACTH-(1-24), up to 10 −4 M, were needed for the displacement of appropriate radiolabelled ligands from dopamine D 1 receptors, serotonin 5-HT 1A , serotonin 5-HT 1B , muscarinic M 1 acetylcholine and histamine H 1 receptors. ACTH-(1-24) also inhibited the binding of [ 3 H]spiperone to dopamine D 2 receptors in membranes of the pituitary gland, the septum and the substantia nigra. ACTH-(1-39) and most ACTH fragments and analogs were less potent than ACTH-(1-24) in displacing [ 3 H]NPA from the dopamine D 2 receptor in striatal membranes. In general there was a relationship between displacing potency and chain length. ACTH-(7-16)-NH 2 and benzyloxycarbonyl-ACTH-(8-16)-NH 2 , however, were more potent than ACTH-(1-24) in reducing the binding of [ 3 H]NPA to dopamine D 2 receptors. ACTH-(7-16)-NH 2 appeared to contain the minimal required amino acid sequence for inhibition of [ 3 H]NPA binding, because a further shortening of the peptide resulted in a marked decrease of inhibitory potency. The present data show that ACTH/MSH-like peptides preferentially interact with dopamine D 2 receptors. |
| Databáze: | OpenAIRE |
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