Muscarinic M₂ receptor promotes vasopressin synthesis in mice supraoptic nuclei

Muscarinic acetylcholine receptors have been suggested to be implicated in arginine-vasopressin secretion because intracerebroventricular muscarinic agonist administration induces arginine-vasopressin release into the circulation. Although which subtype is involved in the regulation of arginine-vasopressin secretion is unclear, M₂ receptors have been reported to be highly expressed in the hypothalamus. In the present study, M₂ receptor-knockout mice were used to elucidate whether M₂ receptor regulates arginine-vasopressin synthesis in the paraventricular nuclei and supraoptic nuclei of the hypothalamus. The number of arginine-vasopressin-immunoreactive neurons in M₂ receptor-knockout mice was significantly decreased in the supraoptic nuclei, but not in the paraventricular nuclei compared with wild-type mice. Plasma arginine-vasopressin level in M₂ receptor-knockout mice was also significantly lower than in the wild-type mice. Urinary volume and frequency as well as water intake in M₂ receptor-knockout mice were significantly higher than those in wild-type mice. The V₂ vasopressin receptor expression in kidneys of M₂ receptor-knockout mice was comparable with that of wild-type mice, and increased urination in M₂ receptor-knockout mice was significantly decreased by administration of desmopressin, a specific V₂ receptor agonist, suggesting that V₂ receptors in the kidneys of M₂ receptor-knockout mice are intact. These results suggest that M₂ receptors promote arginine-vasopressin synthesis in the supraoptic nuclei and play a role in the regulation and maintenance of body fluid.