CHARACTERIZATION OF GALANIN AND 5-HT1A RECEPTOR COUPLING TO ADENYLYL-CYCLASE IN DISCRETE REGIONS OF THE RAT-BRAIN

We have studied the coupling of galanin and 5-HT1A receptors with aden ylyl cyclase in the hypothalamus, the entorhinal cortex and the hippoc ampus of the rat brain. Furthermore, we have evaluated the effects of simultaneous activation of galanin and 5-HT1A receptors on adenylyl cy clase activity. Galanin-(1-29) and galanin-(1-15) showed a dose-depend ent inhibitory effect on forskolin-stimulated adenylyl cyclase activit y in the hypothalamus and entorhinal cortex. No clear effects were obs erved in the hippocampus. Neither galanin-(1-29) nor galanin-(1-15) ha d any effect on the basal activity of adenylyl cyclase in these region s. The selective 5-HT1A receptor agonist 8-OH-2-(di-n-propylamino)-tet ralin (8-OH-DPAT) induced a dose-dependent inhibition of forskolin sti mulated adenylyl cyclase activity in the hippocampus and the entorhina l cortex. 5-HT induced an inhibition in the hypothalamus. In all regio ns the effects could be fully counteracted by methiothepin. 5-HT was s hown to stimulate the basal activity of adenylyl cyclase in the hippoc ampus and the entorhinal cortex. The effects could be counteracted by methiothepin. When galanin-(1-29) and 5-HT/8-OH-DPAT were incubated si multaneously additive inhibitory effects, but no synergistic interacti ons, could be observed on the stimulated adenylyl cyclase activity. In conclusion, galanin and 5-HT1A receptors seem to be linked to differe nt independent pools of G proteins, indicating that the previously dem onstrated intramembrane interactions between galanin and 5-HT1A recept ors involve a mechanism not directly related to adenylyl cyclase.