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Acta Physiologica 2011; Volume 202, Supplement 684
The Joint Conference (FAMÉ 2011) of the LXXVth Meeting of the Hungarian Physiological Society, XVIth Meeting of the Hungarian Society of Anatomists, Experimental Section of the Hungarian Society for Experimental and Clinical Pharmacology and Hungarian Society for Microcirculation and Vascular Biology
6/8/2011-6/11/2011
Pécs, Hungary
AMAZINGLY LOW SENSITIVITY OF CHOLINERGIC MOTOR RESPONSES IN THE HUMAN GUT TO MORPHINE
Abstract number: O5
Bartho1 L., Benko1 R., Illenyi2 L., Papp2 A.
Aims:
Morphine and other opioids are known to inhibit gastrointestinal (GI) propulsive motility. Peripheral mechanisms contribute to this effect. Peripherally-acting opioid agonists are used for the treatment of diarrhoea. Moreover, endogenous opioids may play a role in the regulation of GI motility in man. On the basis of the inhibitory action of morphine on acetylcholine (ACh) release in the guinea-pig gut, it is generally assumed that reduction of ACh output plays a role in the GI actions of morphine in man. We set out to test the effect of morphine (3 mM or 1 and 10 mM) on cholinergic excitatory motor responses of longitudinally- or circularly-oriented preparations of human small and large intestinal segments (obtained from surgery).
Methods:
Organ bath technique with electrical field stimulation (EFS) of nerves were used. Cholinergic contractions in the human gut were evoked as follows. (A) Primary cholinergic contraction without drug pretreatment. Longitudinal strips of the appendix (EFS 1-5 Hz) responded with reproducible tonic spasm, while some strips of the small intestine (5 Hz EFS) with either reproducible or decreasing contractions. (B) Contractions of the small intestine (longitudinal) to EFS (0.5-5 Hz) in the presence of an inhibitor of NO synthase + a P2Y purinoceptor antagonist (for reducing "NANC" inhibition). These responses showed a decrease upon repeated EFS. (C) Cholinergic contraction to 1-Hz EFS in the presence of the cholinesterase inhibitor physostigmine (circular strips of small and large intestine).
Results:
Quantitative results from (A) or (B) indicate no inhibitory effect of morphine (see Pharmacology, 2010, 86:145–148). Also with (C), no obvious inhibitory action of morphine (3 mcM) was found in preliminary experiments.
Conclusions:
Cholinergic motoneurons of the human intestine show amazingly low (if any) sensitivity towards morphine (as compared with the guinea-pig gut). The peripheral effects of morphine on motility may be exerted at other types of neuron/tissue.
Support:
ETT and OTKA grants
To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 202, Supplement 684 :O5