Stimulation of rainbow trout gallbladder contraction by cionin, an ancestral member of the CCK/gastrin family.
Cionin--from the protochordate Ciona intestinalis--is a putative ancestor of cholecystokinin (CCK) and gastrin. Being sulfated on tyrosine in positions 7 and 6 (from the C-terminus), characteristic for CCK and gastrin, respectively, cionin is a structural hybrid of the two peptides. The effects of cionin have previously been characterized in mammalian systems. This study examined a phylogenetically ancient CCK receptor, the rainbow trout (Oncorhynchus mykiss) gallbladder receptor, utilizing cionin, sulfated and nonsulfated CCK and gastrin, and the receptor antagonists L-364,718 and L-365,260. The sulfated peptides induced concentration-dependent contractions of isolated strips of gallbladder with equal efficacy and similar potencies [ED50: 42 (cionin), 23 (CCK-8-s), and 74 nM (gastrin-17-s)], significantly different from the nonsulfated forms [ED50: 1.7 (CCK-8-ns) and 1.9 microM (gastrin-17-ns)]. Ten micromolar L-364,718 and L-365,260 both weakly but significantly inhibited cionin-CCK-8-s, and gastrin-17-s-induced contractions. L-365,260 shifted the concentration response curves 1 1/2 decades to the right and L-364,718 only 1/2 decade. The results confirm that the rainbow trout gallbladder CCK receptor does not distinguish sulfated CCK from sulfated gastrin as do modern CCKA receptors, but does distinguish sulfated from nonsulfated forms of both. However, for optimal effect the receptor does not require a double-sulfated peptide like cionin as might be expected from the lack of selectively between CCK and gastrin. Finally, studies with antagonists known to be specific for either CCK or gastrin receptors in mammalian systems indicate that this ancient receptor behaves more like a mammalian CCKB receptor than as a CCKA receptor.
Schjoldager
B
B
Department of Gynecology and Obstetrics, Rigshospitalet, University of Copenhagen, Denmark.
Jørgensen
J C
JC
Johnsen
A H
AH
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D005704:Gallbladder / Q000502:physiology*; D005755:Gastrins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000737:chemistry / Q000494:pharmacology*; D017686:Oncorhynchus mykiss / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology
D005755:Gastrins; D009479:Neuropeptides; C063059:cionin; D012844:Sincalide