The rabbit motilin receptor: molecular characterisation and pharmacology.

Abstract:

: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 (pEC50=9.25). After transfection with Go1alpha, motilin similarly stimulated [35S]GTPgammaS binding (pEC50=8.87). Using both systems, similar values were obtained with the human receptor, with rank-order potencies of motilin=[Nle13]-motilin>erythromycin; ghrelin was ineffective. In circular muscle preparations of rabbit gastric antrum, [Nle13]-motilin 0.1-30 nM concentration-dependently increased the amplitude of electrically-evoked, neuronally-mediated contractions (pEC50=8.3); higher concentrations increased the muscle tension (30-3000 nM). Both responses to [Nle13]-motilin faded rapidly during its continual presence. Rat or human ghrelin 0.01-10 microM were without activity. Erythromycin 30-3000 nM and 10 microM, respectively, increased neuronal activity and muscle tension in rabbit stomach. Unlike [Nle13]-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, [Nle13]-motilin and erythromycin are distinguished by different response kinetics, reflecting different rates of ligand degradation and/or interaction with the receptor.

journal_name

Br J Pharmacol

authors

Dass NB,Hill J,Muir A,Testa T,Wise A,Sanger GJ

doi

10.1038/sj.bjp.0705505

subject

Has Abstract

pub_date

2003-11-01 00:00:00

pages

948-54

issue

5

eissn

0007-1188

issn

1476-5381

pii

sj.bjp.0705505

journal_volume

140

pub_type

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