Distinct angiotensin II receptor in primary cultures of glial cells from rat brain.

Abstract

Angiotensin II (Ang-II) has profound effects on the brain. Receptors for Ang-II have been demonstrated on neurons, but no relationship between glial cells and Ang-II has been established. Glial cells (from the hypothalamus and brain stem of 1-day-old rat brains) in primary culture have been used to demonstrate the presence of specific Ang-II receptors. Binding of 125I-Ang-II to glial cultures was rapid, reversible, saturable, and specific for Ang-II. The rank order of potency of 125I-Ang-II binding was as follows: Ang-II = [sarcosine1,Ala8]Ang-II greater than [sarcosine1,Ile8]Ang-II much greater than Ang-III greater than Ang-I. Scatchard analysis revealed a homogeneous population of high-affinity (Kd = 1.1 nM) binding sites with a Bmax of 110 fmol/mg of protein. Light-microscopic autoradiography of 125I-Ang-II binding supported the kinetic data, documenting specific Ang-II receptors on the glial cells. Ang-II stimulated a dose-dependent hydrolysis of phosphatidylinositols in glial cells, an effect mediated by Ang-II receptors. However, Ang-II failed to influence [3H]norepinephrine uptake, and catecholamines failed to regulate Ang-II receptors, effects that occur in neurons. These observations demonstrate the presence of specific Ang-II receptors on the glial cells in primary cultures derived from normotensive rat brain. The receptors are kinetically similar to, but functionally distinct from, the neuronal Ang-II receptors.