The rabbit motilin receptor: molecular characterisation and pharmacology

Following identification of the human motilin receptor, we isolated the rabbit orthologue by PCR amplification and found this to be 85% identical to the open reading frame of the human receptor. The protein encoded was 84% identical to the human polypeptide. In HEK293T cells transfected with the rabbit receptor, motilin concentration‐dependently increased intracellular calcium mobilisation ( p EC 50 =9.25). After transfection with G o1 α , motilin similarly stimulated [ 35 S]GTP γ S binding ( p EC 50 =8.87). Using both systems, similar values were obtained with the human receptor, with rank‐order potencies of motilin=[Nle 13 ]‐motilin>erythromycin; ghrelin was ineffective. In circular muscle preparations of rabbit gastric antrum, [Nle 13 ]‐motilin 0.1–30 n M concentration‐dependently increased the amplitude of electrically‐evoked, neuronally‐mediated contractions ( p EC 50 =8.3); higher concentrations increased the muscle tension (30–3000 n M ). Both responses to [Nle 13 ]‐motilin faded rapidly during its continual presence. Rat or human ghrelin 0.01–10 μ M were without activity. Erythromycin 30–3000 n M and 10 μ M , respectively, increased neuronal activity and muscle tension in rabbit stomach. Unlike [Nle 13 ]‐motilin, the increase in neuronal activity did not fade during continual presence of submaximally‐effective concentrations of erythromycin; some fade was observed at higher concentrations. We conclude that the pharmacology of the rabbit motilin receptor is similar to the human orthologue and, when expressed as a recombinant, comparable to the native receptor. However, in terms of their ability to increase neuronal activity in rabbit stomach, [Nle 13 ]‐motilin and erythromycin are distinguished by different response kinetics, reflecting different rates of ligand degradation and/or interaction with the receptor.British Journal of Pharmacology (2003) 140 , 948–954. doi: 10.1038/sj.bjp.0705505