Differential reversal of drug-induced small bowel paralysis by cerulein and neostigmine.
OBJECTIVE
Cerulein and neostigmine are prokinetic drugs whose potency and effective dose range are barely known. The aim of this study was to assess their benefit for normal and compromised peristalsis.


METHODS
In vitro, isolated segments of guinea pig small intestine. Setting : University laboratory.


METHODS
Small bowel segments were mounted in tissue baths and luminally perfused with Tyrode solution. Test drugs (prokinetic: cerulein, neostigmine; inhibitory: atropine, hexamethonium, epinephrine, sufentanil) were added to the tissue bath.


RESULTS
Peristalsis was quantified via changes in the peristaltic pressure threshold. One-way and two-way analysis of variance (ANOVA) were used for statistical analysis. Cerulein (0.03-100 nM) stimulated normal peristalsis in a concentration-dependent manner and reversed paralysis of peristalsis induced by all inhibitory test drugs to a similar extent. The properistaltic effect of neostigmine was limited to a narrow concentration range (0.03-0.1 micro M), whereas concentrations >0.3 micro M inhibited peristalsis. Neostigmine more effectively counteracted blockage of peristalsis caused by atropine than that caused by hexamethonium. The inhibitory effects of epinephrine and sufentanil on peristalsis were reversed only at the concentration range of 0.1-0.3 micro M neostigmine.


CONCLUSIONS
Cerulein stimulates normal peristalsis in vitro at a wide concentration range and reverses blockage of peristalsis caused by drugs with a site of action either on the enteric nervous system or intestinal smooth muscle. Neostigmine's prokinetic effect, to the contrary, is limited to a small concentration range and best seen when peristalsis is depressed by blockage of cholinergic muscle activation.
Fruhwald
Sonja
S
Department of Anaesthesiology and Intensive Care Medicine, University of Graz, Auenbruggerplatz 29, 8036 Graz, Austria. sonja.fruhwald@meduni-graz.at
Herk
Eva
E
Hammer
Heinz F
HF
Holzer
Peter
P
Metzler
Helfried
H
D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006168:Guinea Pigs; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009388:Neostigmine / Q000494:pharmacology*; D010243:Paralysis / Q000139:chemically induced / Q000517:prevention & control; D010277:Parasympathomimetics / Q000494:pharmacology*; D010528:Peristalsis / Q000187:drug effects*; D017409:Sufentanil / Q000494:pharmacology
D000759:Adjuvants, Anesthesia; D000322:Adrenergic Agonists; D005730:Ganglionic Blockers; D010277:Parasympathomimetics; D009388:Neostigmine; D018738:Hexamethonium; D001285:Atropine; D002108:Ceruletide; D017409:Sufentanil; D004837:Epinephrine