Effect of muscarinic receptor modulators in the hypothalamic supraoptic nucleus of the rat.

Abstract

Muscarinic antagonists were injected into the hypothalamic supraoptic nucleus (SON) and their effects on the acetylcholine (ACh) release of this nucleus were studied by in vivo microdialysis techniques. Atropine, AF-DX116 (a M2-receptor antagonist), 4-DAMP (a M3-receptor antagonist) and pirenzepine (a M1-receptor antagonist) concentration-dependently increased the ACh release. The EC50 values for these antagonists were 15 nM for atropine, 7.8 microM for pirenzepine, 0.39 microM for AF-DX116 and 59 nM for 4-DAMP, suggesting the autoregulation of the ACh release through an activation of M2 and M3 subtypes of muscarinic receptors in the SON. The postsynaptic effect of muscarinic receptors on urine outflow was studied by microinjection of selective muscarinic receptor agonists and antagonists into the SON. McN-A-343 (a M1-receptor agonist) had no significant effect on urine outflow. Pre-microinjection of atropine, 4-DAMP, p-F-HHSiD (a M3-receptor antagonist) or pirenzepine into the SON concentration-dependently attenuated the oxotremorine-induced antidiuresis. In contrast, AF-DX116 and methoctramine had no effect on this oxotremorine-induced action. These results suggest that the M3-subtype may contribute to the antidiuretic actions. Nicotine produced an increase in ACh release in the SON and also induced potent antidiuretic effects, both of which were inhibited by hexamethonium. Thus, in the SON, the ACh release may be autoregulated by M2- and M3-subtypes of muscarinic receptors and the antidiuretic effects of ACh produced through an activation of the M3-subtype.