GUINEA-PIG GALLBLADDER AND PANCREAS POSSESS IDENTICAL CCK-A RECEPTOR SUBTYPES - RECEPTOR CLONING AND EXPRESSION

Cholecystokinin (CCK) receptors mediate pancreatic acinar secretion an d gallbladder contraction. Pharmacological and functional studies in p ancreas and gallbladder demonstrate a CCK-A receptor subtype in both t issues. However, some pharmacological studies and affinity cross-linki ng studies of CCK receptors on pancreatic acini and gallbladder sugges t that these two tissues possess two different subtypes of the CCK-A r eceptor. We cloned these receptors in guinea pig using a cDNA clone of the CCK-A receptor from rat pancreas. The guinea pig gallbladder CCK- A receptor was cloned by hybridization screening of a gallbladder cDNA library using a cDNA probe from the rat CCK-A receptor coding region. The guinea pig pancreas CCK-A receptor cDNA was cloned via the polyme rase chain reaction using primers corresponding to the guinea pig gall bladder CCK-A receptor 5'- and 3'-noncoding regions. CCK-A receptor cl ones from guinea pig pancreas and gallbladder had identical nucleotide sequences, which were 80% homologous to the rat CCK-A receptor cDNA s equence. The deduced amino acid sequence from guinea pig CCK-A recepto rs was 89% homologous to the rat CCK-A receptor sequence. Dose-inhibit ion binding studies of transiently expressed receptors by CCK agonists and antagonists exhibited a CCK-A receptor pharmacologically similar to the rat CCK-A receptor. These studies indicate that the CCK-A recep tors in guinea pig pancreas and gallbladder are identical and do not s upport previous proposals that they may represent different receptor s ubtypes.