Pharmacological characterization of alpha adrenoceptor-mediated motor responses in the rat colon.

Background: Inhibitory neuromuscular transmission in the gastrointestinal tract is mediated by intrinsic nitrergic and purinergic neurons. Purines activate G protein-coupled receptor P2Y ₁ receptors, increasing intracellular Ca ²⁺ that activates small conductance calcium-activated potassium (SK _Ca ) 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.
Methods: Muscle bath experiments were performed with the rat proximal, mid, and distal colon oriented both circularly and longitudinally.
Results: The α ₁ -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) (α ₁ -adrenoceptor blocker), and RS17053 (10 ^-6  M) (α _1A -blocker), but not by yohimbine (10 ^-6  M) (α ₂ -adrenoceptor blocker). Apamin (10 ^-6  M), a SK _Ca channel blocker, abolished PE-induced relaxations.
Conclusions: Contractile responses in the circular muscle of the mid colon could be attributed to α-adrenoceptors located on enteric cholinergic neurons. Stimulation of α _1A -adrenoreceptors activates SK _Ca channels to cause smooth muscle relaxation, which constitutes a signaling pathway that shares similarities with P2Y ₁ receptors.
(© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)