Dynamic properties of I2-receptors

Abstract

Evidence is presented that drug binding to I2-sites in the guinea pig kidney and liver is subjected to dynamic homeotropic allosteric regulation. Drugs have been found that are capable of inducing both positive and negative cooperativity on both kidney and liver I2-sites when studied in competition with [3H]idazoxan. Moreover the kinetics of [3H]idazoxan association with guinea pig kidney I2-sites was complex and occurred with three different rate constants. However, on dissociation of [3H]idazoxan from its binding sites in the kidney a substantial number of the slower sites had been converted to faster sites, thus supporting the idea of a dynamic interconversion of I2 sites. The guinea pig liver and kidney I2-sites appear to be similar in their pharmacological properties. They also bear some resemblance to the I2-sites of the smooth muscle of the guinea pig ileum, but they appear to be more distant to the guinea pig cerebral cortex I2-sites. Nevertheless, data indicate that considerable overall heterogeneity exists between the guinea pig kidney and liver I2-sites and the guinea pig ileum and cerebral cortex I2-sites.