Modulation of hypothalamic norepinephrine release by atrial natriuretic peptide: involvement of cyclic GMP

Abstract

The ability of atrial natriuretic peptide (ANP) to modulate K +-stimulated release of [ 3H]norepinephrine ([ 3H]NE) from rat hypothalamic slices was investigated. ANP-(1–28) significantly decreased K +-stimulated [ 3H]NE release in a concentration-dependent manner (maximal inhibition = 22% of control with 100 nM, ED 50 = 70 pM). Pretreatment with pertussis toxin did not alter the response to ANP. 8Br-cGMP (10 μM), a cGMP analog, significantly decreased [ 3H]NE release and when combined with 10 nM ANP-(1–28), an additive effect was observed. Additionally, 3-isobutyl 1-methylxanthine (IBMX) (200 μM), a phosphodiesterase inhibitor, combined with ANP-(1–28) 10 nM, significantly decreased [ 3H]NE release. These results indicate that ANP-(1–28) modulated release of [ 3H]NE from rat hypothalamic slices and the effect is most likely mediated by elevation of intraneuronal cGMP.