Molecular pharmacology
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Molecular pharmacology · Mar 1995
Signal transduction pathways for B1 and B2 bradykinin receptors in bovine pulmonary artery endothelial cells.
Bovine pulmonary artery endothelial (CPAE) cells respond to bradykinin, and it has been suggested that the receptors on these cells do not fall into the normal B1/B2 classification of bradykinin receptors [J. Pharmacol. Exp. ⋯ Pretreatment with the B1 agonist did not inhibit responses evoked by subsequent challenges with either des-Arg9-bradykinin or bradykinin. These results provide pharmacological evidence for the existence of two distinct bradykinin receptor subtypes (B1 and B2) on CPAE cells, with no evidence for heterologous desensitization. Although both subtypes operated similar signal transduction pathways, the Ca2+ responses evoked by the two receptors could be differentiated by NiCl2.
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Molecular pharmacology · Mar 1995
Chronic neurosteroid treatment produces functional heterologous uncoupling at the gamma-aminobutyric acid type A/benzodiazepine receptor complex in mammalian cortical neurons.
We have investigated the effects of chronic treatment with the neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one (5 alpha 3 alpha) on the gamma-aminobutyric acid (GABA)A receptor complex in cultured mammalian cortical neurons. Chronic 5 alpha 3 alpha treatment (up to 2 microM, 5 days) did not produce any changes in the morphological appearance or the cell protein content of cortical neurons. The basal binding of [3H]flunitrazepam, [3H]Ro15-1788, and [3H]Ro15-4513 was not altered after the chronic treatment. ⋯ The EC50 value for GABA-induced 36Cl- influx was not altered, whereas the Emax value was decreased after chronic 5 alpha 3 alpha treatment. Furthermore, the 5 alpha 3 alpha-induced uncoupling was reversed by concomitant exposure of the cortical neurons to 5 alpha-pregnan-3 beta-ol-20-one or R5135, suggesting an involvement of the neurosteroid and GABA recognition sites in the observed uncoupling. Taken together, these results suggest that chronic 5 alpha 3 alpha treatment produces heterologous uncoupling at the GABAA receptor complex.