Corpus Cavernosal Smooth Muscle Relaxation Effect of a Novel AMPK Activator, Beta-Lapachone
- Authors
- Bae, Jae Hyun; Kim, Jin Wook; Kweon, Gi Ryang; Park, Myoung Gyu; Jeong, Kyeong-Hoon; Kim, Je Jong; Moon, Du Geon
- Issue Date
- 8월-2011
- Publisher
- WILEY-BLACKWELL
- Keywords
- AMPK Activator; Beta-Lapachone; Penile Erection; eNOS; Corpus Cavernosum; Smooth Muscle Relaxation
- Citation
- JOURNAL OF SEXUAL MEDICINE, v.8, no.8, pp.2205 - 2214
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF SEXUAL MEDICINE
- Volume
- 8
- Number
- 8
- Start Page
- 2205
- End Page
- 2214
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/134223
- DOI
- 10.1111/j.1743-6109.2010.01809.x
- ISSN
- 1743-6095
- Abstract
- Introduction. Adenosine monophosphate-activated protein kinase (AMPK) activation is suggested to relax smooth muscle by endothelial nitric oxide synthase (eNOS) phosphorylation. Aim. To assess the mechanism and effect of a novel AMPK activator, beta-lapachone, upon cavernosal smooth muscle relaxation and the therapeutic potential for erectile dysfunction. Methods. Human umbilical vein endothelial cells (HUVECs) were treated with beta-lapachone. The lysates were blotted with specific antibodies for phosphorylated AMPK (p-AMPK) or phosphorylated eNOS (p-eNOS). The membranes were re-blotted for total AMPK total eNOS, or beta-actin. The eNOS activity was measured by the conversion of L-14C-arginine to L-14C-citrulline in HUVECs lysates. In a separated experiment, cavernosal strips from New Zealand white rabbits were harvested for organ bath study and the relaxation effect of beta-lapachone on phenylephrine-induced contracted strips was evaluated and compared with sodium nitroprusside, zaprinast, metformin, and aminoimidazole carboxamide ribonucleotide (AICAR). Methylene blue and L-NAME were used to assess the inhibition of cyclic guanosine monophosphate/nitric oxide pathway. Zinc-protoporphyrin-IX (ZnPP) was also used to investigate the contribution of mevalonate pathway. Main Outcome Measures. The expression of p-AMPK, p-eNOS, AMPK and eNOS induced by beta-lapachone in HUVECs study and the percent relaxation of cavernosal tissue in organ bath study. Results. Beta-lapachone clearly induced AMPK phosphorylation and, as a consequence, eNOS phosphorylation in HUVECs. Beta-lapachone-induced upregulation of eNOS activity was also observed in HUVECs and steadily increased up to 1 hour. In organ bath study, beta-lapachone significantly relaxed the phenylephrine pretreated strips in a dose-dependent manner. This relaxation effect was not totally blocked by methylene blue or L-NAME. After removing endothelium, the relaxation was totally blocked by ZnPP. Conclusions. A novel AMPK activator, beta-lapachone has a strong relaxation effect on precontracted cavernosal smooth muscle strips in the rabbit. And phosphorylation of AMPK and eNOS strongly related to the action of beta-lapachone. Mevalonate pathway also might be considered as a suggestive mechanism. Bae JH, Kim JW, Kweon GR, Park MG, Jeong K-H, Kim JJ, and Moon DG. Corpus cavernosal smooth muscle relaxation effect of a novel AMPK activator, beta-lapachone. J Sex Med 2011;8:2205-2214.
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