The Inhibitory Effect of Papaverine on Respiration-Dependent Contracture of Guinea Pig Taenia Coli in High-K Medium. Iii. The Differential Effect of Papaverine and Rotenone on Dt Diaphorase

Abstract

Abstract-The differential effects of papaverine (Pap) and rotenone (Rot) were studied on the highly respiration-dependent contracture of guinea pig taenia coli in 40 mM potassium (40-K) medium, on isolated DT diaphorase activity and on mitochondrial respiration.The inhibition of guinea pig taenia coli to the 40-K induced tension by Rot (5 x 10-7 M) was fully reversed by the addition of a water soluble vitamin K3 (VK3) derivative or menadione sodium bisulfite (MSB). A low concentration (10-'-10-6 M) of Pap which had no effect on the 40-K induced tension inhibited the VK3 restored tension from the Rot suppression, corresponding to a Pap inhibition of the isolated DT diaphorase.Inhibition of the effective concentration of Pap to the 40-K induced tension development was never reversed by addition of VK3 or MSB. In taenia coli, both MSB and VK3 established a bypass of the Rot sensitive site on the mitochondrial respiratory chain by means of the DT diaphorase system. The difference in washout efficacy between Pap and Rot on the inhibition of 40-K induced tension was ascribed to a difference in their mitochondria) binding properties.

The Inhibitory Effect of Papaverine on Respiration-Dependent Contracture of Guinea Pig Taenia Coli in High-K Medium. Ii. Inhibition of Mitochondrial Respiration

“…As shown in MSB had almost no effect on the Rot inhibition of respiration by taenia coil Mt , while MSB and vitamin K3 both reversed the Rot inhibition in rat liver Mt (16). Therefore, the taenia coli Mt prepared by the protease method may contain a small quantity of DT diaphorase .…”

Effects of Papaverine on Twitches in Mouse Diaphragm

“…Some studies have reported the possibility that the mechanisms underlying papaverine-associated relaxation involve the inhibition of mitochondrial respiration [4][5][6][7][8] . Tsuda et al [6][7][8] showed that papaverine inhibited high K + -induced contraction and O 2 consumption in guinea pig taenia coli and inhibited mitochondrial respiration by blocking the transduction of electrons between NADH and coenzyme Q and by inhibiting NADH and NADHP-diaphorase.…”

“…Tsuda et al [6][7][8] showed that papaverine inhibited high K + -induced contraction and O 2 consumption in guinea pig taenia coli and inhibited mitochondrial respiration by blocking the transduction of electrons between NADH and coenzyme Q and by inhibiting NADH and NADHP-diaphorase. Conversely, Ozaki et al [38] reported that the high K + -induced contraction was accompanied by an increase in FPox fluorescence or PNred fluorescence in guinea pig taenia coli.…”

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tracellular accumulation of cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) by inhibiting phosphodiesterase (PDE) [1][2][3] ; (2) inhibition of mitochondrial respiration [4][5][6][7][8] , and (3) effects on Ca 2+ movement [9] . Although these different mechanisms have been proposed, efforts to compare and evaluate the 3 concepts in various smooth muscles have been neglected.

We recently reported that papaverine inhibits smoothmuscle contraction mainly by the accumulation of cAMP and/or cGMP due to the inhibition of PDE in tonic muscle, such as rat aorta [10] and bovine trachea [11] , but by inhibiting mitochondrial respiration in phasic muscle, such as guinea pig ileum [10] , urinary bladder [12] and rat uterus [13] .

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Effects of papaverine on carbachol- and high K⁺-induced contraction in the bovine abomasum

“…The relaxing mechanism of papaverine, a non-selective smooth muscle relaxant, has been previously explained as the follows: 1) it inhibits phosphodiesterase (PDE) and results in an intracellular accumulation of cAMP and/or cGMP [ 22 , 25 , 32 ], 2) it inhibits mitochondrial respiration [ 26 , 27 , 33 , 34 , 35 ] and 3) it results in the effects on Ca 2+ movement [ 13 ]. Although these different mechanisms have been proposed by respected researchers, there were no previous studies comparing and evaluating these three mechanisms in various smooth muscles.…”