Underlying mechanisms involved in progesterone-induced relaxation to the pig bladder neck

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• 作者：V铆tor S. Fern ; es ; Ana S.F. Ribeiro ; Ana Mart铆nez-S谩enz ; Igor Blaha ; Daniel Serrano-Marg眉ello ; Paz Recio ; Ana Cristina Mart铆nez ; Salvador Bustamante ; David V谩zquez-Alba ; Joaqu铆n Carballido ; Albino Garc铆a-Sacrist谩n ; Medardo Hern谩ndez
• 关键词：4-AP ; 4-aminopyridine ; COX ; cyclooxygenase ; IbTX ; iberiotoxin ; TRAM 34 ; 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole ; KATP ; ATP-dependent K+ ; BKCa ; large conductance Ca2+-activated K+ channels ; IKCa ; intermediate conductance Ca2+-activated K+ ; SKCa ; small conductance Ca2+-activated K+ ; KV ; voltage-gated K+ channels ; l-NOARG ; NG-nitro-l-arginine ; NO ; nitric oxide ; ODQ ; 1H-[1 ; 2 ; 4]-oxadiazolo[4 ; 3-a]quinoxalin-1-one ; PhE ; phenylephrine ; VOC ; voltage-gated Ca2+
• 刊名：European Journal of Pharmacology
• 出版年：15 January, 2014
• 年：2014
• 卷：723
• 期：Complete
• 页码：246-252
• 全文大小：1110 K

文摘

Progesterone increases bladder capacity and improves the bladder compliance by its relaxant action on the detrusor. A poor information, however, exists concerning to the role of this steroid hormone on the bladder outflow region contractility. This study investigates the progesterone-induced action on the smooth muscle tension of the pig bladder neck. To this aim, urothelium-denuded bladder neck strips were mounted in myographs for isometric force recordings and for simultaneous measurements of intracellular Ca²⁺ concentration ([Ca²⁺]_i) and tension. On phenylephrine (PhE)-precontracted strips, progesterone produced concentration-dependent relaxations only at high pharmacological concentrations. The blockade of progesterone receptors, nitric oxide (NO) synthase, guanylyl cyclase, large conductance Ca²⁺-activated K⁺ (BK_Ca) or ATP-dependent K⁺ (K_ATP) channels reduced the progesterone relaxations. The presence of the urothelium and the inhibition of cyclooxygenase (COX), intermediate- and small-conductance Ca²⁺-activated K⁺ channels failed to modify these responses. In Ca²⁺-free potassium rich physiological saline solution, progesterone inhibited the contraction to CaCl₂ and to the L-type voltage-operated Ca²⁺ (VOC) channel activator BAY-K 8644. Relaxation induced by progesterone was accompanied by simultaneous decreases in smooth muscle [Ca²⁺]_i. These results suggest that progesterone promotes relaxation of pig bladder neck through smooth muscle progesterone receptors via cGMP/NO pathway and involving the activation of BK_Ca and K_ATP channels and inhibition of the extracellular Ca²⁺ entry through L-type VOC channels.