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• Twenty-nine amino acids at the N-terminus of wild-type Gαq were replaced by the corresponding sequence in Gαi1 to facilitate the binding of scFv16.

Cholecystokinin (CCK) receptor family belongs to class-A sevenfold transmembrane G protein-coupled receptors, and is divided into CCK1 receptor (CCK1R) and CCK2 receptor (CCK2R)1. CCK1R is mainly distributed in the gastrointestinal tract2,3,4, peripheral nervous system5,6, and some regions of the brain, e.g., the area postrema, the nucleus tractus solitarius, and the hypothalamus7,8,9,10. Hence, CCK receptors (CCKRs) regulate a variety of physiological functions including digestion, satiety, emotion regulation, pain sensation, and memory process18,19,20,21,22,23,24,25. Besides, CCKRs are expressed in the brain–gut axis which is a region critical for the transmission of information between gut and brain including satiation signals. For these functions, there are already some specific drugs designed for CCK1R, such as ceruletide, or for CCK2R, including proglumide and pentagastrin. Although all of them have been used for gastrointestinal diseases, they and some drugs under clinical trial also have the potential to treat CNS diseases, including pain and anxiety26,27.

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CCK peptides release insulin and glucagon more potently in man and pig than in dog and rat (51, 85–87). The difference is partly due to neurons in pancreatic islets that release CCK-8 and CCK-5 in man and pig (51), whereas rat and dog islets have no such innervation (50, 51). Moreover, islet cells in man and pig also express the CCK2 receptor abundantly (73), whereas rat islet cells express mainly the CCK1 receptor (88). While the interest in the effect of CCK on the exocrine pancreas was for many years restricted to enzyme secretion, it is now well established that CCK also stimulates fluid and bicarbonate secretion.

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