Erythromycin inhibits rabbit pyloric smooth muscle through neuronal motilin receptors. 1996

H P Parkman, and A P Pagano, and J P Ryan
Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.

OBJECTIVE Erythromycin's effect in accelerating gastric emptying is attributed primarily to increased antral contractility. The aim of this study was to characterize erythromycin's effect on pyloric muscle. METHODS Rabbit pyloric muscle strips were studied in vitro. RESULTS Pyloric muscle strips developed spontaneous phasic contractions with a frequency of 1.9 +/- 0.1 contractions per minute. Erythromycin and motilin had dose-dependent inhibitory effects on pyloric muscle. At the maximal effective dose (50 mumol/L), erythromycin caused cessation of spontaneous contractions for 1.8 +/- 0.2 minutes, decreasing the initial 2-minute motility index to 35% +/- 9% (P < 0.01) of basal. In the presence of tetrodotoxin, both erythromycin and motilin increased pyloric contractility. Motilin tachyphylaxis both in the presence or absence of tetrodotoxin abolished the effects of erythromycin. The inhibitory effect of erythromycin was decreased by NG-nitro-L-arginine methyl ester and the vasoactive intestinal peptide antagonist [4-Chloro-D-Phe6, Leu17]vasoactive intestinal peptide. CONCLUSIONS These studies suggest that motilin receptors are present on both pyloric muscle and inhibitory neurons to pyloric muscle, that the primary effect of erythromycin on the pylorus is mediated by activating motilin receptors on inhibitory motor neurons, and that both nitric oxide and vasoactive intestinal peptide may mediate the inhibitory effect of erythromycin.

UI MeSH Term Description Entries
D009037 Motilin A peptide of about 22-amino acids isolated from the DUODENUM. At low pH it inhibits gastric motor activity, whereas at high pH it has a stimulating effect.
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011708 Pylorus The region of the STOMACH at the junction with the DUODENUM. It is marked by the thickening of circular muscle layers forming the pyloric sphincter to control the opening and closure of the lumen. Pyloric Sphincter,Pyloric Sphincters,Sphincter, Pyloric,Sphincters, Pyloric
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D011964 Receptors, Gastrointestinal Hormone Cell surface proteins that bind gastrointestinal hormones with high affinity and trigger intracellular changes influencing the behavior of cells. Most gastrointestinal hormones also act as neurotransmitters so these receptors are also present in the central and peripheral nervous systems. Gastrointestinal Hormone Receptors,Intestinal Hormone Receptors,Receptors, Gastrointestinal Peptides,Gastrointestinal Hormone Receptor,Intestinal Hormone Receptor,Receptors, Gastrointestinal Hormones,Receptors, Intestinal Hormone,Gastrointestinal Hormones Receptors,Gastrointestinal Peptides Receptors,Hormone Receptor, Gastrointestinal,Hormone Receptor, Intestinal,Hormone Receptors, Gastrointestinal,Hormone Receptors, Intestinal,Hormones Receptors, Gastrointestinal,Peptides Receptors, Gastrointestinal,Receptor, Gastrointestinal Hormone,Receptor, Intestinal Hormone
D004917 Erythromycin A bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Erycette,Erymax,Erythromycin A,Erythromycin C,Erythromycin Lactate,Erythromycin Phosphate,Ilotycin,T-Stat,Lactate, Erythromycin,Phosphate, Erythromycin,T Stat,TStat
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013618 Tachyphylaxis Rapidly decreasing response to a drug or physiologically active agent after administration of a few doses. In immunology, it is the rapid immunization against the effect of toxic doses of an extract or serum by previous injection of small doses. (Dorland, 28th ed)

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