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 adenylyl cyclase in the hypothalamus, the entorhinal cortex and the hippocampus of the rat brain. Furthermore, we have evaluated the effects of simultaneous activation of galanin and 5-HT1A receptors on adenylyl cyclase activity. Galanin-(1-29) and galanin-(1-15) showed a dose-dependent inhibitory effect on forskolin-stimulated adenylyl cyclase activity in the hypothalamus and entorhinal cortex. No clear effects were observed in the hippocampus. Neither galanin-(1-29) nor galanin-(1-15) had any effect on the basal activity of adenylyl cyclase in these regions. The selective 5-HT1A receptor agonist 8-OH-2-(di-n-propylamino)-tetralin (8-OH-DPAT) induced a dose-dependent inhibition of forskolin stimulated adenylyl cyclase activity in the hippocampus and the entorhinal cortex. 5-HT induced an inhibition in the hypothalamus. In all regions the effects could be fully counteracted by methiothepin. 5-HT was shown to stimulate the basal activity of adenylyl cyclase in the hippocampus and the entorhinal cortex. The effects could be counteracted by methiothepin. When galanin-(1-29) and 5-HT/8-OH-DPAT were incubated simultaneously additive inhibitory effects, but no synergistic interactions, could be observed on the stimulated adenylyl cyclase activity. In conclusion, galanin and 5-HT1A receptors seem to be linked to different independent pools of G proteins, indicating that the previously demonstrated intramembrane interactions between galanin and 5-HT1A receptors involve a mechanism not directly related to adenylyl cyclase.
Billecocq
A
A
Unit of Neuroimmunoendocrinological Pharmacology, Institut Pasteur, Paris, France.
Hedlund
P B
PB
Bolaños-Jiménez
F
F
Fillion
G
G
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018728:Entorhinal Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D019004:Galanin; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D009479:Neuropeptides; D010446:Peptide Fragments; D010455:Peptides; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D011985:Receptors, Serotonin; D005576:Colforsin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019004:Galanin; D000262:Adenylyl Cyclases