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

Abstract 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.