“…On the other hand, stimulation of G i/o -coupled receptors, including GABA B receptor, dopamine D 2 receptor, or ␣ 2 adrenoceptor, has been shown to enhance cAMP production induced by G s -coupled receptors such as  2 -adrenoceptor and vasoactive intestinal peptide receptor (9, 12, 23, 30). Some G i/o -coupled receptors, including opioid receptor, ␣ 2 -adrenoceptor, muscarinic M 4 receptor, and cannabinoid CB 1 receptor, are coupled not only to G i/o protein but also to G s protein and are known to stimulate cAMP production (5,7,8,11). We have shown in this study that 5-HT-induced enhancement of ISO-and PACAP38-mediated responses was abrogated by pretreatment with PTX in oocytes expressing CFTR,  2 -adrenoceptor, or PACAP receptor together with 5-HT 1A R. Because PTX interrupts signaling pathways from G i/o -coupled receptors to G i/o proteins without affecting G s protein-mediated responses (9), we conclude that G i/o proteins, but not G s proteins, are involved in such enhancement.…”