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Effects Of Endomorphin-1 And -2 On μ-Opioid Receptors In Myenteric Neurons And In The Peristaltic Reflex In Rat Small Intestine

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1. The aim of the present investigations was to characterize the effect of endomorphins on the function of rat small intestine smooth muscle and on the electrically induced ascending and descending reflex pathway of rat small intestine in vitro.

2. Endomorphin-1 and -2 left the basal tonus and the pharmacologically stimulated smooth muscle unchanged. In contrast, electrically induced twitch contractions were significantly reduced by endomorphin-1 and -2 and this reduction was reversed by the μ-opioid receptor antagonist Cys-Tyr-Orn-Pen-amide (CTOP), suggesting a specific μ-opioid receptor-mediated effect on neural tissue.

3. In the reflex model, endomorphin-1 caused a significant inhibition (IC50 2.3 × 10–8 mol/L) of the ascending contraction (10–8 mol/L: –28.3 ± 5.8%; 10–7 mol/L: –94.7 ± 0.2.8%; both P < 0.05; n = 7). Descending relaxation increased at a concentration of 10–8 mol/L endomorphin-1 (+61.6 ± 24.5%; 10–7 mol/L: +237.0 ± 65.4%; both P < 0.05; n = 6).

4. Endomorphin-1 caused a further significant increase in the latency of the ascending contraction (10–8 mol/L: +44.7 ± 20.5%; 10–7mol/L: +93.5 ± 16.1%; both P < 0.05; n = 7), whereas the latency of the descending relaxation was unaltered (n = 7). Similar results were observed for endomorphin-2.

5. All effects could be reversed by a wash-out afterwards and were blocked by pre-incubation with CTOP (10–6 mol/L).

6. Reverse transcription–polymerase chain reaction demonstrated mRNA expression of μ-opioid receptors in the rat ileum longitudinal muscle/myenteric plexus preparation, as well as in the oesophagus and stomach.

7. Endomorphin-1 and -2 reduce the cholinergic-induced contractile response of the rat ileal smooth muscle preparation via a presynaptic mechanism.

8. By a specific and reversible interaction with μ-opioid receptors, the ascending excitatory and descending inhibitory reflex responses were attenuated or facilitated, respectively.

9. In conclusion, the endomorphins may be the physiological endogenous μ-opioid receptor agonists in the rat small intestine.
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Keywords: endomorphin-1; endomorphin-2; peristaltic reflex; μ-opioid receptors

Document Type: Research Article

Affiliations: II Medizinische Klinik und Poliklinik der TU München, München, Germany

Publication date: May 1, 2002

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