Intracerebroventricular (ICV) microinjection of a selective kappa opioid agonist increases inducible cAMP element repressor (ICER) expression in the supraoptic nucleus of conscious rats.

Abstract

Central and peripheral administration of kappa (κ) opioid agonists, U-50488H (U-50), in conscious rats produces a water free diuresis via central inhibition of vasopressin (AVP). Activation of κ receptors has been associated with the inhibition of cyclic AMP accumulation, which may stimulate the expression of endogenous transcriptions factors involved in suppression of cyclic AMP (i.e., ICER). The goal of this study is to examine central κ-mediated changes in ICER staining in the two CNS sites involved in AVP secretion, the paraventricular nuclei (PVN) and supraoptic nucleus (SON). Urine samples were collected during control (15-min) and after ICV vehicle (VEH, n=8) or U-50 (10 μg; n= 8). 3 additional urine samples (15-min) were collected after the ICV injection. The forebrain was processed for ICER using polyclonal anti-ICER antibody raised in rabbit. In VEH injected rats, renal excretion of water or sodium was not altered. U-50 produced a rapid and marked increase in urine flow and decrease in urinary sodium excretion rate. In addition, ICV U-50 produced significant increases in ICER staining in the SON (VEH, 15 ± 8; U-50 33 ± 9; P < .05) without increasing ICER in the PVN (VEH, 26 ± 13; U-50, 22 ± 10; P < .05). In the SON, double labeling shows that 80% of the ICER positive cells were AVP neurons. These results indicate that 1) ICV U-50 injections are associated with differential changes in ICER expression in SON versus PVN magnocellular neurons 2) the diuretic effects of U-50 may be mediated by the inhibition of SON AVP secreting neurons. Supported by NIH HL62579 & DK57822.