GR138676, a novel peptidic tachykinin antagonist which is potent at NK3 receptors
| Autor: | J.M. Stables, Dominic M. Walsh, S. Arkinstall, R.M. Hagan, P. Ward, I.J.M. Beresford, P.W. Seale, S.J. Ireland |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Agonist medicine.medical_specialty Neurokinin B medicine.drug_class Molecular Sequence Data CHO Cells Astrocytoma Substance P Biology Pharmacology Transfection Binding Competitive Cellular and Molecular Neuroscience chemistry.chemical_compound Endocrinology Cricetinae Internal medicine Tumor Cells Cultured medicine Radioligand Animals Humans Amino Acid Sequence Receptor Arachidonic Acid Portal Vein Endocrine and Autonomic Systems Chinese hamster ovary cell Antagonist Receptors Neurokinin-3 Receptors Neurokinin-2 General Medicine Receptors Neurokinin-1 Peptide Fragments Rats HYDIA Neurology chemistry Competitive antagonist Calcium Oligopeptides |
| Zdroj: | Neuropeptides. 27:333-341 |
| ISSN: | 0143-4179 |
| DOI: | 10.1016/0143-4179(94)90059-0 |
| Popis: | GR138676, a conformationally constrained analogue of neurokinin B, is a novel, potent NK3 receptor antagonist. GR138676 was a competitive antagonist of neurokinin B-dependent arachidonic acid mobilization from prelabelled Chinese hamster ovary cells stably transfected with a human NK3 receptor gene (pKB 8.3) and of contractions induced by senktide in rat portal vein (pKB 8.2). However, GR138676 was also a competitive antagonist of the increase in intracellular calcium evoked by the selective NK1 agonist, GR73632, in the human astrocytoma U373MG cell-line (pKB 8.3). GR138676 had little activity at NK2 receptors, inhibiting binding of the NK2 antagonist radioligand [3H]-GR100679 to Chinese hamster ovary cells transfected with the human ileum NK2 receptor with a pKi of 6.0. In summary, despite its activity at NK1 receptors, GR138676 will be a useful tool for characterizing NK3 receptors as well as defining the physiological and pathophysiological function of this receptor subtype. |
| Databáze: | OpenAIRE |
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