CCK-X receptors in the endothermic mako shark (Isurus oxyrinchus).
By mapping the distribution of cholecystokinin (CCK) receptor types onto an established phylogenetic hypothesis of vertebrate relationships, we tested two hypothesis about the evolution of CCK receptors: (1) A single CCK receptor type, CCK-X, is the ancestral receptor, while CCK-A and CCK-B receptors represent derived receptor types; (2) the evolution of two separate CCK receptors is functionally related to the evolution of endothermy. Specifically, we localized and characterized 125I-CCK-binding sites in the gut and brain of mako shark (Isurus oxyrinchus), a warm-blooded chondrichthyean fish. Competitive inhibition studies of 125I-CCK binding showed that the CCK receptor in the mako shark brain, gallbladder, pyloric stomach, and intestine binds sulfated CCK-8 and sulfated gastrin-17 (gastrin-17-II) with much higher affinity (K(i) ranging from 0.05 to 2.02 nM) than unsulfated gastrin-17 (gastrin-17-I, K(i) ranging from 4.63 to 62.17 nM). These results indicate that the mako shark expresses a single CCK-X receptor in all tissues. Additional competitive inhibition studies showed that the mako CCK-X receptor has very low affinities for the following nonpeptide agonist and antagonists: A71623, L364,718, A57696, A65186.72, Cam-1481, and SR 27897B (specific for some mammalian CCK-A receptors) and L365,260 and CI-988 (specific for some mammalian CCK-B receptors), confirming the pharmacological differences between the CCK-X receptor and the CCK-A and -B receptors. Based on the mapped phylogenetic distribution of CCK receptor types, we conclude that CCK-X is the ancestral receptor type and that two receptor types, e.g. CCK-A and CCK-B, are not part of the suite of characters necessary for evolution of endothermy in fishes.
Oliver
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Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Vigna
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D000818:Animals; D001665:Binding Sites; D001833:Body Temperature Regulation / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology*; D004064:Digestive System / Q000737:chemistry*; D019143:Evolution, Molecular; D005704:Gallbladder / Q000737:chemistry*; D007422:Intestines / Q000737:chemistry; D011706:Pyloric Antrum / Q000737:chemistry; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000032:analysis* / Q000187:drug effects; D012754:Sharks / Q000378:metabolism*
C104399:CCK-X receptor; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin