Excitatory action of vasopressin in the brain of the rat: role of cAMP signaling.

Brain vasopressin plays a role in behavioral and cognitive functions and in pathological conditions. Relevant examples are pair bonding, social recognition, fear responses, stress disorders, anxiety and depression. At the neuronal level, vasopressin exerts its effects by binding to V1a receptors. In the brainstem, vasopressin can excite facial motoneurons by generating a sustained inward current which is sodium-dependent, tetrodotoxin-insensitive and voltage-gated. This effect is independent of intracellular calcium mobilization and is unaffected by phospholipase Cβ (PLCβ) or protein kinase C (PKC) inhibitors. There are two major unsolved problems. (i) What is the intracellular signaling pathway activated by vasopressin? (ii) What is the exact nature of the vasopressin-sensitive cation channels? We performed recordings in brainstem slices. Facial motoneurons were voltage-clamped in the whole-cell configuration. We show that a major fraction, if not the totality, of the peptide effect was mediated by cAMP signaling and that the vasopressin-sensitive cation channels were directly gated by cAMP. These channels appear to exclude lithium, are suppressed by 2-aminoethoxydiphenylborane (2-APB) and flufenamic acid (FFA) but not by ruthenium red or amiloride. They are distinct from transient receptor channels and from cyclic nucleotide-regulated channels involved in visual and olfactory transduction. They present striking similarities with cation channels present in a variety of molluscan neurons. To our knowledge, the presence in mammalian neurons of channels having these properties has not been previously reported. Our data should contribute to a better knowledge of the neural mechanism of the central actions of vasopressin, and may be potentially significant in view of clinical applications.