Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Herbert, MK; Weis, R; Holzer, P; Roewer, N.
Peristalsis in the Guinea pig small intestine in vitro is impaired by acetaminophen but not aspirin and dipyrone.
ANESTH ANALG. 2005; 100: 120-127.
Doi: 10.1213/01.ANE.0000139352.54676.18
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- Führende Autor*innen der Med Uni Graz
- Herbert Michael K.
- Co-Autor*innen der Med Uni Graz
- Holzer Peter
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- Abstract:
- Inhibition of intestinal peristalsis is a major side effect of opioid analgesics. It is unknown whether non-opioid analgesics, such as acetaminophen, acetylsalicylic acid, and dipyrone, exert any effect on intestinal motility. In the current in vitro study we examined the effect of these analgesics on intestinal peristalsis and analyzed some of their mechanisms of action. In isolated segments of the guinea pig small intestine peristalsis was triggered by a perfusion-induced increase of the intraluminal pressure. The peristaltic pressure threshold (PPT) at which peristaltic waves were elicited was used to quantify drug effects on peristalsis. Vehicle (Tyrode's solution), acetaminophen (0.01-100 microM), acetylsalicylic acid (100-300 microM), and dipyrone (10-100 microM) were added extraserosally to the organ bath. Acetaminophen concentration-dependently increased PPT and abolished peristalsis in four of six segments at the concentration of 10 microM and in all segments tested at 100 microM (EC50=6.0 microM). The increase in PPT resulting from 3 microM acetaminophen was reduced by naloxone and apamin but not changed by L-nitro-arginine methylester (L-NAME), its inactive enantiomer D-NAME, acetylsalicylic acid, methysergide, or tropisetron. Acetylsalicylic acid and dipyrone did not affect peristalsis. The results reveal, for the first time, that acetaminophen concentration-dependently impairs intestinal peristalsis, whereas acetylsalicylic acid and dipyrone lacked such an effect. The inhibition caused by acetaminophen involves transmitters acting via small conductance Ca2+-activated potassium channels, endogenous opioidergic pathways, and presumably inhibition of cyclooxygenase-3.
- Find related publications in this database (using NLM MeSH Indexing)
- Acetaminophen - pharmacology
- Analgesics, Non-Narcotic - pharmacology
- Animals - pharmacology
- Anti-Inflammatory Agents, Non-Steroidal - pharmacology
- Aspirin - pharmacology
- Comparative Study - pharmacology
- Dipyrone - pharmacology
- Dose-Response Relationship, Drug - pharmacology
- Electrophysiology - pharmacology
- Enzyme Inhibitors - pharmacology
- Female - pharmacology
- Guinea Pigs - pharmacology
- In Vitro - pharmacology
- Indoles - pharmacology
- Intestine, Small - drug effects
- Male - drug effects
- Methysergide - pharmacology
- NG-Nitroarginine Methyl Ester - pharmacology
- Naloxone - pharmacology
- Narcotic Antagonists - pharmacology
- Nitric Oxide Synthase - antagonists and inhibitors
- Peristalsis - drug effects
- Serotonin Antagonists - pharmacology