Full and partial agonist activity of C-terminal cholecystokinin peptides at the cloned human CCK-A receptor expressed in Chinese hamster ovary cells.
The agonist activities of the C-terminal cholecystokinin peptides sulfated cholecystokinin octapeptide (CCK-8S), non-sulfated cholecystokinin octapeptide (CCK-8NS), pentagastrin and CCK-4 at the cloned human CCK-A receptor expressed in Chinese hamster ovary cells were evaluated in two functional assays of receptor activation. [125I]-CCK-8S displacement studies employing membranes derived from these cells revealed the expected rank order of affinity for a number of CCK receptor ligands. CCK-8S was a potent agonist in (i) stimulating the mobilization of intracellular free Ca2+, measured with the Ca2+ sensitive fluorescent indicator FURA-2, and (ii) stimulating increases in extracellular acidification rates, measured by microphysiometry. Consistent with their lower affinities for CCK-A receptors, CCK-8NS, pentagastrin and CCK-4 were weaker agonists in both functional assays. In addition, these peptides exhibited partial agonist activity relative to the maximum response observed with CCK-8S in both assays. These results demonstrate that CCK-8S represents the minimum ligand requirement for both high affinity and full agonist activity at the human CCK-A receptor subtype.
Dunlop
J
J
Wyeth-Ayerst Research, Princeton, NJ 08540, USA. Dunlopj@war.wyeth.com
Zhang
Y
Y
Evans
N
N
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism; D001667:Binding, Competitive; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D020109:Devazepide; D006727:Hormone Antagonists / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010418:Pentagastrin / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011377:Proglumide / Q000031:analogs & derivatives / Q000378:metabolism; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012844:Sincalide / Q000031:analogs & derivatives* / Q000378:metabolism*; D013758:Tetragastrin / Q000378:metabolism*
C090019:8-sulfocholecystokinin octapeptide; D001570:Benzodiazepinones; D006727:Hormone Antagonists; D010446:Peptide Fragments; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; D010418:Pentagastrin; D011377:Proglumide; D020109:Devazepide; C048181:lorglumide; D012844:Sincalide; D002118:Calcium