Anti-emetic and emetic effects of erythromycin in Suncus murinus: Role of vagal nerve activation, gastric motility stimulation and motilin receptors

Farideh A. Javid, David C. Bulmer, John Broad, Qasim Aziz, George E. Dukes, Gareth J. Sanger

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Paradoxically, erythromycin is associated with nausea when used as an antibiotic but at lower doses erythromycin activates motilin receptors and is used to treat delayed gastric emptying and nausea. The aim of this study was to characterise pro- and anti-emetic activity of erythromycin and investigate mechanisms of action. Japanese House musk shrews (Suncus murinus) were used. Erythromycin was administered alone or prior to induction of emesis with abnormal motion or subcutaneous nicotine (10 mg/kg). The effects of erythromycin and motilin on vagal nerve activity and on cholinergically mediated contractions of the stomach (evoked by electrical field stimulation) were studied in vitro. The results showed that erythromycin (1 and 5 mg/kg) reduced vomiting caused by abnormal motion (e.g., from 10.3±1.8 to 4.0±1.1 emetic episodes at 5 mg/kg) or by nicotine (from 9.5±2.0 to 3.1±2.0 at 5 mg/kg), increasing latency of onset to emesis; lower or higher doses had no effects. When administered alone, erythromycin 100 mg/kg induced vomiting in two of four animals, whereas lower doses did not. In vitro, motilin (1, 100 nM) increased gastric vagal afferent activity without affecting jejunal afferent mesenteric nerve activity. Cholinergically mediated contractions of the stomach (prevented by tetrodotoxin 1 μM or atropine 1 μM, facilitated by l-NAME 300 μM) were facilitated by motilin (1-100 nM) and erythromycin (10-30 μM). In conclusion, low doses of erythromycin have anti-emetic activity. Potential mechanisms of action include increased gastric motility (overcoming gastric stasis) and/ or modulation of vagal nerve pathways involved in emesis, demonstrated by first-time direct recording of vagal activation by motilin.

LanguageEnglish
Pages48-54
Number of pages7
JournalEuropean Journal of Pharmacology
Volume699
Issue number1-3
DOIs
Publication statusPublished - 15 Jan 2013

Fingerprint

Emetics
Antiemetics
Erythromycin
Stomach
Motilin
Vomiting
Nicotine
Nausea
Shrews
Gastroparesis
motilin receptor
Gastric Emptying
Tetrodotoxin
Atropine
Electric Stimulation
Action Potentials
Anti-Bacterial Agents

Cite this

Javid, Farideh A. ; Bulmer, David C. ; Broad, John ; Aziz, Qasim ; Dukes, George E. ; Sanger, Gareth J. / Anti-emetic and emetic effects of erythromycin in Suncus murinus : Role of vagal nerve activation, gastric motility stimulation and motilin receptors. In: European Journal of Pharmacology. 2013 ; Vol. 699, No. 1-3. pp. 48-54.
@article{461c38c60e5c4cb697add577a4f64646,
title = "Anti-emetic and emetic effects of erythromycin in Suncus murinus: Role of vagal nerve activation, gastric motility stimulation and motilin receptors",
abstract = "Paradoxically, erythromycin is associated with nausea when used as an antibiotic but at lower doses erythromycin activates motilin receptors and is used to treat delayed gastric emptying and nausea. The aim of this study was to characterise pro- and anti-emetic activity of erythromycin and investigate mechanisms of action. Japanese House musk shrews (Suncus murinus) were used. Erythromycin was administered alone or prior to induction of emesis with abnormal motion or subcutaneous nicotine (10 mg/kg). The effects of erythromycin and motilin on vagal nerve activity and on cholinergically mediated contractions of the stomach (evoked by electrical field stimulation) were studied in vitro. The results showed that erythromycin (1 and 5 mg/kg) reduced vomiting caused by abnormal motion (e.g., from 10.3±1.8 to 4.0±1.1 emetic episodes at 5 mg/kg) or by nicotine (from 9.5±2.0 to 3.1±2.0 at 5 mg/kg), increasing latency of onset to emesis; lower or higher doses had no effects. When administered alone, erythromycin 100 mg/kg induced vomiting in two of four animals, whereas lower doses did not. In vitro, motilin (1, 100 nM) increased gastric vagal afferent activity without affecting jejunal afferent mesenteric nerve activity. Cholinergically mediated contractions of the stomach (prevented by tetrodotoxin 1 μM or atropine 1 μM, facilitated by l-NAME 300 μM) were facilitated by motilin (1-100 nM) and erythromycin (10-30 μM). In conclusion, low doses of erythromycin have anti-emetic activity. Potential mechanisms of action include increased gastric motility (overcoming gastric stasis) and/ or modulation of vagal nerve pathways involved in emesis, demonstrated by first-time direct recording of vagal activation by motilin.",
keywords = "Erythromycin, Gastric motility, Motilin, Suncus murinus, Vagus, Vomiting",
author = "Javid, {Farideh A.} and Bulmer, {David C.} and John Broad and Qasim Aziz and Dukes, {George E.} and Sanger, {Gareth J.}",
year = "2013",
month = "1",
day = "15",
doi = "10.1016/j.ejphar.2012.11.035",
language = "English",
volume = "699",
pages = "48--54",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-3",

}

Anti-emetic and emetic effects of erythromycin in Suncus murinus : Role of vagal nerve activation, gastric motility stimulation and motilin receptors. / Javid, Farideh A.; Bulmer, David C.; Broad, John; Aziz, Qasim; Dukes, George E.; Sanger, Gareth J.

In: European Journal of Pharmacology, Vol. 699, No. 1-3, 15.01.2013, p. 48-54.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anti-emetic and emetic effects of erythromycin in Suncus murinus

T2 - European Journal of Pharmacology

AU - Javid, Farideh A.

AU - Bulmer, David C.

AU - Broad, John

AU - Aziz, Qasim

AU - Dukes, George E.

AU - Sanger, Gareth J.

PY - 2013/1/15

Y1 - 2013/1/15

N2 - Paradoxically, erythromycin is associated with nausea when used as an antibiotic but at lower doses erythromycin activates motilin receptors and is used to treat delayed gastric emptying and nausea. The aim of this study was to characterise pro- and anti-emetic activity of erythromycin and investigate mechanisms of action. Japanese House musk shrews (Suncus murinus) were used. Erythromycin was administered alone or prior to induction of emesis with abnormal motion or subcutaneous nicotine (10 mg/kg). The effects of erythromycin and motilin on vagal nerve activity and on cholinergically mediated contractions of the stomach (evoked by electrical field stimulation) were studied in vitro. The results showed that erythromycin (1 and 5 mg/kg) reduced vomiting caused by abnormal motion (e.g., from 10.3±1.8 to 4.0±1.1 emetic episodes at 5 mg/kg) or by nicotine (from 9.5±2.0 to 3.1±2.0 at 5 mg/kg), increasing latency of onset to emesis; lower or higher doses had no effects. When administered alone, erythromycin 100 mg/kg induced vomiting in two of four animals, whereas lower doses did not. In vitro, motilin (1, 100 nM) increased gastric vagal afferent activity without affecting jejunal afferent mesenteric nerve activity. Cholinergically mediated contractions of the stomach (prevented by tetrodotoxin 1 μM or atropine 1 μM, facilitated by l-NAME 300 μM) were facilitated by motilin (1-100 nM) and erythromycin (10-30 μM). In conclusion, low doses of erythromycin have anti-emetic activity. Potential mechanisms of action include increased gastric motility (overcoming gastric stasis) and/ or modulation of vagal nerve pathways involved in emesis, demonstrated by first-time direct recording of vagal activation by motilin.

AB - Paradoxically, erythromycin is associated with nausea when used as an antibiotic but at lower doses erythromycin activates motilin receptors and is used to treat delayed gastric emptying and nausea. The aim of this study was to characterise pro- and anti-emetic activity of erythromycin and investigate mechanisms of action. Japanese House musk shrews (Suncus murinus) were used. Erythromycin was administered alone or prior to induction of emesis with abnormal motion or subcutaneous nicotine (10 mg/kg). The effects of erythromycin and motilin on vagal nerve activity and on cholinergically mediated contractions of the stomach (evoked by electrical field stimulation) were studied in vitro. The results showed that erythromycin (1 and 5 mg/kg) reduced vomiting caused by abnormal motion (e.g., from 10.3±1.8 to 4.0±1.1 emetic episodes at 5 mg/kg) or by nicotine (from 9.5±2.0 to 3.1±2.0 at 5 mg/kg), increasing latency of onset to emesis; lower or higher doses had no effects. When administered alone, erythromycin 100 mg/kg induced vomiting in two of four animals, whereas lower doses did not. In vitro, motilin (1, 100 nM) increased gastric vagal afferent activity without affecting jejunal afferent mesenteric nerve activity. Cholinergically mediated contractions of the stomach (prevented by tetrodotoxin 1 μM or atropine 1 μM, facilitated by l-NAME 300 μM) were facilitated by motilin (1-100 nM) and erythromycin (10-30 μM). In conclusion, low doses of erythromycin have anti-emetic activity. Potential mechanisms of action include increased gastric motility (overcoming gastric stasis) and/ or modulation of vagal nerve pathways involved in emesis, demonstrated by first-time direct recording of vagal activation by motilin.

KW - Erythromycin

KW - Gastric motility

KW - Motilin

KW - Suncus murinus

KW - Vagus

KW - Vomiting

UR - http://www.scopus.com/inward/record.url?scp=84871867820&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2012.11.035

DO - 10.1016/j.ejphar.2012.11.035

M3 - Article

VL - 699

SP - 48

EP - 54

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

ER -