Effects of hypocretin 1 on cyclic AMP formation in primary neuronal cell cultures from rat cerebral cortex

• Published in: Acta neurobiologiae experimentalis Vol. 69; no. 1; p. 99
• Main Authors: Zawilska, J B, Woldan-Tambor, A, Urbanska, A
• Format: Journal Article
• Language: English
• Published: 01.01.2009
• ISSN: 0065-1400

Hypocretin 1 and hypocretin 2 (Hcrt; also called orexin-A and orexin-B, respectively) are two newly discovered neuropeptides synthesized in the hypothalamus. Besides playing a role in the control of arousal and wake-sleep cycle, both hypocretins have been reported to exert diverse physiological actions, including central regulation of feeding and energy homeostasis, regulation of cardiovascular and autonomic functions, and of the neuroendocrine system. The physiological effects of hypocretins are mediated via two G-protein coupled receptors, Hcrtr-1 and Hcrtr-2. Hcrtr-2 receptor has equal affinity for both Hcrtl and Hcrt2, whist Hcrtr-2 receptor has ten-fold greater affinity for Hcrt1 than for Hcrt2. Despite of several studies, relatively little is known about hypocretin receptors signaling in different tissues. Here we show effects of Hcrtl on cyclic AMP formation in primary neuronal cultures from rat cerebral cortex. Hcrtl used at 0.01-1 mu M concentrations did not exert significant actions on the basal cyclic AMP formation in primary cultures from rat cerebral cortex. Hctr1 inhibited, in a concentration-dependent manner, increases in cyclic AMP accumulation evoked by the incubation of neuronal cultures with for-skolin (a direct activator of adenylyl cyclase; 1 and 3 mu M), pituitary adenylate cyclase-activating polypeptide (PACAP27; 0.1 micromolar) or with vasoactive intestinal peptide (VIP; 3 mu M). The obtained results indicate that Hcrtr in rat cortical neurons couples through Gi subclass of G-proteins, and suggest the presence of a neuron-linked functional interaction between hypocretins and neuropeptides PACAP/VIP.