Table 2.

Mutagenesis of vasopressin/oxytocin receptors and its influence on oxytocin binding

Mutated Receptor/Cell SystemMutationResidue in hOTR*Expression LevelAffinity for OTReference Nos.
hOTR/HeLaN8D8>100%Unaltered 296
hOTR/HeLaN15D15>100%Unaltered 296
hOTR/HeLaN15/26D15/26VariableUnaltered 296
hOTR/HeLaN8/26D8/26VariableUnaltered 296
hOTR/COS-7N57A57No binding, no signaling 166
hOTR/COS-7D85A85<10%No binding, no signaling (low affinity for AVP) 166
hOTR/COS-7D85N85No binding, no signaling 587
hOTR/COS-7D85E85NDDecreased 7-fold (for OTA: increased 10-fold) 587
rV1aR/COS-7D97A85100%Decreased >12-fold 398
rV1aR/COS-7Q104A92100%Decreased >6-fold 398
rV1aR/COS-7Q108A96100%Decreased >12-fold 398
pV2R/COS.M6Y102F103200%Increased 2-fold 463
pV2R/COS.M6Y102D103NDDecreased >30-fold 562
pV2R/COS.M6Y102N103NDDecreased 3-fold 562
bV2R/COS.M6D103Y10350%Unaltered 562
rV1aR/COS-7Y115F103NDIncreased 19-fold 105
hV1aR/COS-7Y115F103NDIncreased 8-fold 105
rV1aR/COS-7Y115D103NDUnaltered 105
rV1aR/COS-7Y115L103NDDecreased 2.4-fold 105
pV2R/COS.M6R105Y10650%Decreased 1.4-fold
bV2R/COS.M6R106L10660%Unaltered 562
hOTR/COS-7G107A107NDUnaltered 587
rV1aR/COS-7K128A11650%Decreased >6-fold 398
rV1aR/COS-7Q131A119100%Decreased >12-fold 398
hOTR/COS-7D136A136No binding, no signaling 166
hOTR/COS-7D136Q136No binding, no signaling 166
hOTR/COS-7R137A13710%Decreased 1.8-fold (constitutively active) 166
rV1aR/COS-7Q185A171150%Decreased >12-fold 398
pV2R/COS.M6E197Q19350%Unaltered
rV1aR/COS-7T223A205100%Increased 2.6-fold 398
hOTR/COS-7Y209F20950%Increased 2.5-fold (for OTA: decreased 40-fold) 106
hOTR/COS-7Y209A209No binding, no signaling 106
hOTR/COS-7F284Y28485%Unaltered 106
hOTR/COS-7F284A284No binding, no signaling 106
hOTR/COS-7F293I293NDUnaltered 587
rV1aR/COS-7Q317A29550%Decreased >6-fold 398
rOTR/CHO-K1C351S346100%Unaltered 241
rOTR/CHO-K1C352S347100%Unaltered 241
  • The receptor mutants are characterized by the receptor type (for abbreviations, see legend to Fig. 3; species: r, rat; h, human; p, pig), the cell line in which the receptor has been expressed, and the name of the mutation using single-letter code for amino acids and numbering of residues according to their primary sequence (e.g., in the mutant N15, 26D, the asparagines at positions 15 and 26 in the human OT receptor have been mutated to aspartates). * The indicated residues represent the equivalent positions of the mutagenized amino acid within the human OT receptor (hOTR) (see Figs. 4 and 5, alignment in Fig. 3). The expression levels are given in percent of expression of the corresponding wild-type receptor. ND, not determined. † Postina and Fahrenholz, unpublished data.