Characterisation of a cloned human 5-HT1A receptor cell line using [35S]GTP gamma S binding.
Eur J Pharmacol
; 320(2-3): 267-75, 1997 Feb 12.
Article
em En
| MEDLINE
| ID: mdl-9059863
ABSTRACT
Compound potencies and efficacies depend upon receptor reserve and hence estimating this parameter in assay systems allows for a more meaningful interpretation of the data generated. This study describes a method whereby the degree of receptor reserve, with respect to 5-hydroxytryptamine (5-HT), was determined for a HeLa cell line expressing the human 5-HT1A receptor using the agonist-induced [35S]guanosine 5'[gamma-thio]triphosphate ([35S]GTP gamma S) binding assay, followed by a comparison of the potencies and relative efficacies of several compounds. Following irreversible antagonism with benextramine 5-HT yielded a pKA of 7.3, compared with a pKobs of 8.4 from saturation analysis, indicating the presence of high and low affinity state receptors. A 20% receptor occupancy elicited a half-maximal functional response consistent with the presence of receptor reserve. 5-HT, 5-carboxamidotryptamine (5-CT), 8-hydoxy-dipropylamino-tetralin (8-OH-DPAT), 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1 H-indole (RU24969), buspirone, gepirone, mesulergine and sumatriptan were equally efficacious. 1-(2-Methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN 190) displayed reduced relative efficacy and methiothepin inverse agonism.
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Base de dados:
MEDLINE
Assunto principal:
Guanosina 5'-O-(3-Tiotrifosfato)
/
Receptores de Serotonina
Limite:
Humans
Idioma:
En
Ano de publicação:
1997
Tipo de documento:
Article