Prostaglandins mediate tonic contraction of the guinea pig and human gallbladder

The gallbladder (GB) maintains tonic contraction modulated by neurohormonal inputs but generated by myogenic mechanisms. The aim of these studies was to examine the role of prostaglandins in the genesis of GB myogenic tension. Muscle strips and cells were treated with prostaglandin agonists, antagonists, cyclooxygenase (COX) inhibitors, and small interference RNA (siRNA). The results show that PGE(2), thromboxane A(2) (TxA(2)), and PGF(2 alpha) cause a dose-dependent contraction of muscle strips and cells. However, only TxA(2) and PGE(2) (E prostanoid 1 receptor type) antagonists induced a dose-dependent decrease in tonic tension. A COX-1 inhibitor decreased partially the tonic contraction and TxB(2) (TxA(2) stable metabolite) levels; a COX-2 inhibitor lowered the tonic contraction partially and reduced PGE(2) levels. Both inhibitors and the nonselective COX inhibitor indomethacin abolished the tonic contraction. Transfection of human GB muscle strips with COX-1 siRNA partially lowered the tonic contraction and reduced COX-1 protein expression and TxB(2) levels; COX-2 siRNA also partially reduced the tonic contraction, the protein expression of COX-2, and PGE(2). Stretching muscle strips by 1, 2, 3, and 4 g increased the active tension, TxB(2), and PGE(2) levels; a COX-1 inhibitor prevented the increase in tension and TxB(2); and a COX-2 inhibitor inhibited the expected rise in tonic contraction and PGE(2). Indomethacin blocked the rise in tension and TxB(2) and PGE(2) levels. We conclude that PGE(2) generated by COX-2 and TxA(2) generated by COX-1 contributes to the maintenance of GB tonic contraction and that variations in tonic contraction are associated with concomitant changes in PGE(2) and TxA(2) levels.