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.