Received for publication September 4, 2007.
Revised November 28, 2007.
Accepted for publication November 28, 2007.

Involvement of P2Y₁ and P2Y₁₁ purinoceptors in parasympathetic inhibition of colonic smooth muscle

Abstract

Purinergic signalling was first recognized in the guinea pig taenia coli, where relaxation of smooth muscle by nerve released ATP may involve the activation of P2Y₁ and P2Y₁₁ receptors and transcripts for both genes have been found. A partial sequence for P2Y₁₁ protein was identified; the full length P2Y₁ sequence has already been described. P2Y₁ and P2Y₁₁ proteins were localised by immunohistochemistry in smooth muscle cells. P2X₂ and P2X₃ proteins were also localised in motoneurons of the myenteric plexus. meATP and BzATP evoked fast relaxations in the taenia, and were inhibited by the P2Y₁ receptor antagonist, MRS2179. However, meATP and BzATP may stimulate neuronal P2X receptors to release ATP which then acts on P2Y₁ receptors. Accordingly, fast relaxations evoked by meATP and BzATP were inhibited by the P2X₃ and P2X_2/3 receptor antagonist, A317491. When P2Y₁, P2X₃ and P2X_2/3 receptors were blocked and adenosine removed enzymatically, meATP and BzATP evoked slow relaxations that were inhibited by Reactive Red. Fast and slow relaxations involve SK_Ca and BK_Ca channels; the latter are dependent on intracellular cyclic AMP levels, which altered the duration and amplitude of relaxations. meATP and BzATP were confirmed as agonists, and Reactive Red as an antagonist, of human P2Y₁₁ receptors. In summary, G_q coupled P2Y₁ receptors are involved mainly in fast relaxations, whereas G_q and G_s coupled P2Y₁₁ receptors are involved in both fast and slow relaxations. These P2Y receptor subtypes, plus neuronal P2X receptors, may explain the phenomenon of parasympathetic inhibition first described by Langley (1898).

Key words: P2Y1 receptor, P2Y11 receptor, noncholinergic, parasympathetic, purinergic, smooth muscle