Alterations in Spleen Norepinephrine and Lymphocyte [ 3H] Dihydroalprenolol Binding Site Number in Genetically Epilepsy-Prone Rats

Abstract

Noradrenergic neurotransmission plays an important role in normal immune reactivity. Genetically epilepsy-prone (GEPR-9) rats exhibit deficits in central noradrenergic systems and diminished plaque-forming cell responses following immunization in vivo. In the present study we examined the hypothesis that immunosuppression in GEPR-9 rats is associated with alterations in the splenic noradrenergic system. The content of norepinephrine (NE) in spleens of GEPR-9 age-matched nonepileptic Sprague–Dawley control rats was determined by high-performance liquid chromatography coupled with electrochemical detection (HPLC–EC). In addition, we measured the number of β-adrenergic receptors on splenic lymphocyte membranes of GEPR-9 and control rats using the β-adrenergic receptor antagonist dihydroalprenolol ([ 3H]DHA). HPLC–EC analysis revealed that splenic norepinephrine content was significantly greater in GEPR-9 rats than in controls. Results from receptor binding studies indicated a 33% reduction in specific binding of [ 3H]DHA to splenic lymphocyte membranes of GEPR-9 rats. Saturation of binding studies revealed a significant decrease in the maximum number of [ 3H]DHA binding sites on splenic lymphocyte membranes from GEPR-9 rats. These results indicate that the noradrenergic system in GEPR-9 rat spleen is altered. Whether either or both of these changes contribute to reduced immune reactivity in GEPR-9 rats remains to be determined.