Neural and muscular receptors for motilin in the rabbit colon

Motilin receptors were classically recognized in the gastroduodenal area, w here they help to regulate interdigestive motility. More recently, motilin receptors were identified in the colon where their biologic significance re mains unclear. We aimed here to characterize the motilin receptors of the r abbit colon. Distal colon and duodenum were obtained from sacrificed rabbit s. Tissues homogenized by Polytron were submitted to differential centrifug ation to obtain neural synaptosomes or smooth muscle plasma membranes enric hed solutions. Motilin binding to these membranes was determined by the dis placement of I-125 MOT by the native peptide MOT 1-22, or by peptide analog ues MOT 1-12 [CH2NH](10-11) or GM-109 and by erythromycin derivative GM-611 . Motilin binding capacity was maximum in colon nerves (49.5 +/- 6.5 fmol/m g protein vs. 19.9 +/- 2.5 in colon muscles or 9.4 +/- 2.8 and 6.6 +/- 1.2 in duodenal muscles and antral nerves respectively); all tissues expressed similar affinity for MOT 1-22, and the motilin agonist GM-611 bound equally to neural or muscle tissues from the rabbit colon; the synthetic antagonis t MOT 1-12 [CH2NH](10-11) showed greater affinity for colon nerves than for colon muscles (pIC50: 7.23 +/- 0.07 vs. 6.75 +/- 0.03). Similar results we re obtained with the peptide antagonist GM-109; receptor affinity toward MO T 1-12 [CH2NH10-11] was always five times superior in neural tissues, wheth er they came from the colon or the antrum, than in muscle tissues, whether they were obtained From colon or from duodenum. Motilin receptors are found in very high concentration in nerves and in muscles from rabbit colon: spe cific motilin receptor subtypes are identified in nerves (N) and muscles (M ) of the rabbit colon; N acid M receptor subtypes seem independent of the o rgan location. (C) 2000 Elsevier Science Inc. All rights reserved.