KMUP‐1 relaxes rabbit corpus cavernosum smooth muscle in vitro and in vivo: involvement of cyclic GMP and K+ channels

Lin, Rong-Jyh; Wu, Bin–Nan; Lo, Yi-Ching; Shen, Kuo-Pyng; Lin, Young-Tso; Huang, Chun‐Hsiung; Chen, Ing‐Jun

doi:10.1038/sj.bjp.0704554

Cited by 40 publications

(47 citation statements)

References 32 publications

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“…[29][30][31] However, in the present investigation, the blockade of K Ca channels (both high Maxi-K and low-conductance K Ca ), with charybdotoxin and apamin, respectively, and the K ATP channels by glibenclamide did not modify significantly the F 3-5 -induced relaxation. These findings suggest that the relaxation effect of F 3-5 is unrelated to Ca 2 þ -activated, ATP-sensitive and voltage-dependent K þ channels.…”

Section: Discussioncontrasting

confidence: 75%

Relaxant effects of an alkaloid-rich fraction from Aspidosperma ulei root bark on isolated rabbit corpus cavernosum

et al. 2007

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We described earlier that an alkaloid-rich fraction (F 3-5 ) from Aspidosperma ulei (Markgr) induces penile erection-like behavioral responses in mice. This study verified a possible relaxant effect of this fraction on isolated rabbit corpus cavernosum (RbCC) strips precontracted by phenylephrine (1 lM) or K þ 60 mM. F 3-5 (1-300 lg ml À1 ) relaxed the RbCC strips in a concentration-dependent and reversible manner. The relaxant effect of F 3-5 (100 lg ml À1 ) on phenylephrine contraction was unaffected in the presence of atropine, N-x-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one and by preincubation with tetrodotoxin, glibenclamide, apamine and charybdotoxin suggesting that mechanisms other than cholinergic, nitrergic, sGC activation or potassium channel opening are probably involved. However, the phasic component of the contraction induced by K þ 60 mM as well as the maximal contraction elicited by increasing external Ca 2 þ concentrations in depolarized corpora cavernosa was inhibited by F 3-5 . We conclude that F 3-5 relaxes the RbCC smooth muscle, at least in part, through a blockade of calcium influx or its function.

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Section: Discussioncontrasting

confidence: 75%

Relaxant effects of an alkaloid-rich fraction from Aspidosperma ulei root bark on isolated rabbit corpus cavernosum

et al. 2007

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“…In addition, the combination of glibenclamide and L-NAME were not additive showing that the NO/ GC/ c GMP pathway is probably linked to the activation of the K ATP -channel, as demonstrated by Lin et al (Figure 6b). 26 The role of K ATP channels in the relaxation of the HCC are being studied and point to a role of K ATP openers as second line alternatives in the management of drug refractory ED. 11,27 The chemical management of phentolamine, as a mother drug, would lead to compounds that could increment NO stimulating and K ATP opening activity keeping the a-adrenergic blocker property.…”

Section: Discussionmentioning

confidence: 99%

Phentolamine relaxes human corpus cavernosum by a nonadrenergic mechanism activating ATP-sensitive K+ channel

et al. 2004

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To investigate the pharmacodynamics of phentolamine in human corpus cavernosum (HCC) with special attention to the role of the K þ channels. Strips of HCC precontracted with nonadrenergic stimuli and kept in isometric organ bath immersed in a modified Krebs-Henseleit solution enriched with guanethidine and indomethacine were used in order to study the mechanism of the phentolamine-induced relaxation. Phentolamine caused relaxation (E50%) in HCC strips precontracted with K þ 40 mM. This effect was not blocked by tetrodotoxin (1 lM) (54.674.6 vs 48.976.4%) or (atropine (10 lM) (52.776.5 vs 58.675.6%). However, this relaxation was significantly attenuated by L-NAME (100 lM) (59.775.8 vs 27.877.1%; Po0.05; n ¼ 8) and ODQ (100 lM) (62.775.1 vs 26.873.9%; Po0.05; n ¼ 8). Charybdotoxin and apamin (K Ca -channel blockers) did not affect the phentolamine relaxations (54.674.6 vs 59.375.2%). Glibenclamide (100 lM), an inhibitor of K ATP -channel, caused a significant inhibition (56.776.3 vs 11.372.3%; Po0.05; n ¼ 8) of the phentolamine-induced relaxation. In addition, the association of glibenclamide and L-NAME almost abolished the phentolamine-mediated relaxation (54.675.6 vs 5.771.4%; Po0.05; n ¼ 8). The results suggest that phentolamine relaxes HCC by a nonadrenergicnoncholinergic mechanism dependent on nitric oxide synthase activity and activation of K ATPchannel.

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“…[22][23][24][25] We used this in vitro system to characterize the relaxant effect of the plant alkaloid SEC and to study the underlying mechanism. SEC showed a concentration-dependent relaxant effect on phenylephrine-precontracted RbCC muscle, with an EC 50 of 13.6 mmol l 21 , which is four times lower than the EC 50 of 52.4 mmol l 21 , which was observed with aortic smooth muscle.…”

Section: Discussionmentioning

confidence: 99%

Relaxant effect and possible mechanism of 17-nor-subincanadine E in rabbit corpora cavernosa

Benvindo¹,

Nascimento²,

Santos³

et al. 2011

Asian J Androl

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Compounds with dual action on cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) may be a treatment option for erectile dysfunction, as they not only promote penile erection but also prevent the upregulation of phosphodiesterase-5. In this study, we examined the possible relaxant effect and mechanism of 17-nor-subincanadine E (SEC, 0.2-200 mmol l 21 ), a plant-derived alkaloid, in rabbit corpus cavernosum (RbCC) strips that had been precontracted by exposure to phenylephrine (10 mmol l 21 ) or a high concentration of K 1 (60 mmol l 21 ) in vitro. In addition to SEC's effect on cAMP and cGMP levels, electrical field stimulation (EFS) in phenylephrine-precontracted RbCC and calcium chloride (1-100 mmol l 21 ) evoked responses in depolarized RbCC were analysed. SEC relaxed the phenylephrine-precontracted RbCCs in a concentration-dependent manner. Atropine, guanethidine and N-v-nitro-L-arginine methyl ester (L-NAME) did not have any effect on the relaxation of RBCCs. When 1H-1,2,4 oxadiazole[4,3-a] quinoxalin-1-one (ODQ) was added, it effectively blocked the relaxant response of SEC. Although SEC enhanced the maximal relaxation produced by sodium nitroprusside (SNP) and forskolin in phenylephrine-precontracted cavernosal smooth muscle, it caused a decrease in the maximal contractile response induced by calcium chloride in depolarized RbCCs. The relaxant effect of SEC was paralleled by an increase in the tissue levels of the cyclic nucleotides cAMP and cGMP. We conclude that SEC promotes the relaxation of RbCC, possibly favouring cAMP and cGMP accumulation and calcium blockade. This novel mechanism could be useful for patients who do not benefit from phosphodiesterase inhibitors and for those with endothelial and nitrergic dysfunction, such as patients with diabetes, hypertension and dyslipidaemias. Asian Journal of Andrology (2011) 13, 747-753; doi:10.1038/aja.2011.41; published online 18 July 2011Keywords: 17-nor-subincanadine E; cyclic nucleotides; electrical field stimulation; nitric oxide; rabbit corpus cavernosum; smooth muscle relaxation INTRODUCTIONThe erect penis has always been a symbol of power, virility and fertility. Erectile dysfunction (ED) is the consistent inability to achieve and maintain an erection sufficient for satisfactory sexual activity. This condition is a complex neurovascular disorder that affects 52% of men aged 40-70 years and causes considerable distress, unhappiness and relationship problems for these men. 1,2 Penile erection occurs as a function of trabecular smooth muscle relaxation and a subsequent increase in blood flow to lacunar spaces, which results in engorgement of the penis and restriction of venous drainage. Basically, the process is mediated by nitric oxide (NO) release from cavernosal nerve varicosities and endothelial cells, and this release activates intracellular guanylate cyclase to produce cGMP. 3 Recently, the selective phosphodiesterase 5 (PDE5) inhibitors sildenafil, tadalafil and vardenafil were shown to enhance the proerectile effect ...

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KMUP‐1 relaxes rabbit corpus cavernosum smooth muscle in vitro and in vivo: involvement of cyclic GMP and K⁺ channels

Cited by 40 publications

References 32 publications

Relaxant effects of an alkaloid-rich fraction from Aspidosperma ulei root bark on isolated rabbit corpus cavernosum

Relaxant effects of an alkaloid-rich fraction from Aspidosperma ulei root bark on isolated rabbit corpus cavernosum

Phentolamine relaxes human corpus cavernosum by a nonadrenergic mechanism activating ATP-sensitive K+ channel

Relaxant effect and possible mechanism of 17-nor-subincanadine E in rabbit corpora cavernosa

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