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| Hauptverfasser: | , , , , , |
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| Format: | Artículo Open Access |
| Veröffentlicht: |
Wiley
2024
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| Schlagworte: | |
| Online-Zugang: | https://onlinelibrary.wiley.com/doi/10.1111/nmo.14921 |
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Inhaltsangabe:
- Pharmacological characterization of alpha adrenoceptor‐mediated motor responses in the rat colon Sara Traserra Marc Grao Sonia Trujillo Francesc Jiménez‐Altayó Patri Vergara Marcel Jimenez Neurogastroenterology & Motility AbstractBackgroundInhibitory neuromuscular transmission in the gastrointestinal tract is mediated by intrinsic nitrergic and purinergic neurons. Purines activate G protein‐coupled receptor P2Y1 receptors, increasing intracellular Ca2+ that activates small conductance calcium‐activated potassium (SKCa) channels. Little is known about the effect of adrenergic receptor activation on intestinal smooth muscle. In vascular tissue, stimulation of α‐adrenoceptors causes smooth muscle contraction, while their effect on intestinal tissue is poorly understood. This study aimed to pharmacologically characterize the effect of α‐adrenoceptor activation in the rat colon, which shares similar inhibitory pathways to the human colon.MethodsMuscle bath experiments were performed with the rat proximal, mid, and distal colon oriented both circularly and longitudinally.ResultsThe α1‐adrenoceptor agonist phenylephrine (PE) (10−8–10−5 M) evoked concentration‐dependent relaxations of the intestinal smooth muscle from all regions and orientations. However, in the mid‐circular colon at low PE concentrations, a contraction sensitive to 10−5 M phentolamine (non‐selective α‐adrenoceptor blocker), the neural blocker tetrodotoxin (TTX; 10−6 M), and atropine (10−6 M) was recorded. PE‐induced relaxations were insensitive to TTX (10−6 M) and the nonselective β‐adrenoceptor blocker propranolol (10−6 M). In contrast, PE‐induced relaxations were blocked by phentolamine (10−5 M), prazosin (10−6 M) (α1‐adrenoceptor blocker), and RS17053 (10−6 M) (α1A‐blocker), but not by yohimbine (10−6 M) (α2‐adrenoceptor blocker). Apamin (10−6 M), a SKCa channel blocker, abolished PE‐induced relaxations.ConclusionsContractile responses in the circular muscle of the mid colon could be attributed to α‐adrenoceptors located on enteric cholinergic neurons. Stimulation of α1A‐adrenoreceptors activates SKCa channels to cause smooth muscle relaxation, which constitutes a signaling pathway that shares similarities with P2Y1 receptors. 10.1111/nmo.14921 http://creativecommons.org/licenses/by-nc-nd/4.0/