Elucidation of the mechanism whereby prostanoid TP receptor stimulation enhances urinary bladder smooth muscle contractions induced by parasympathetic neurotransmitters

Right: Prof. Yoshio Tanaka
2nd from the Right: Mr. Guanghan Ou
3rd fro the Right: Dr. Keisuke Obara
Left Dr. Kento Yoshida

A research group led by Professor Yoshio Tanaka of the Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, has revealed that prostanoid TP receptor stimulation enhanced urinary bladder smooth muscle contractions induced by parasympathetic neurotransmitters, acetylcholine (ACh) and adenosine triphosphate (ATP), and this enhancement could be partly regulated by protein kinase C (PKC). These findings were published in advance in the journal “Journal of Pharmacological Sciences” on August 29, 2023.

A schematic summary of this study. Prostanoid TP receptor stimulation enhances ACh- and ATP-induced urinary bladder smooth muscle (UBSM) contractions through the following possible mechanisms shown as dotted arrow lines. Regarding ATP, TP receptor stimulation could enhance the contractions through 1) PKC-mediated VDCC and purinoceptor (P2X1 receptor) activation, 2) VDCC activation by inhibition of BK channel negative regulation of VDCC, and 3) ROCK-mediated purinoceptor (P2X1 receptor) activation. Regarding ACh, TP receptor stimulation could enhance the contractions through 1) BK channel inhibition-mediated VDCC activation and 2) increase of Ca²⁺ release from the sarcoplasmic reticulum (SR), although involvement of PKC is apparently negligible. This is because TP receptor stimulation could cause PKC-mediated activation of VDCC while it could also cause PKC-mediated suppression of muscarinic receptor (M₃ receptor) function; the latter suppressing effect may counteract the former potentiating effect. Solid red/blue lines show the potentiating/suppressing effects when M₃ receptor or P2X1 receptor is stimulated. Dotted red/blue lines show the potentiating/suppressing effects produced by TP receptor stimulation. TXA₂, thromboxane A2; ACh, acetylcholine; PKC, protein kinase C; VDCC, voltage-dependent Ca²⁺ channel; BK channel, big conductance calcium-activated potassium channel; ROCK, Rho-associated protein kinase.