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| Regulation of intracellular Ca2+ release in corpus cavernosum smooth muscle: synergism between nitric oxide and cGMP |
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| Author(s): Williams BA, Liu CQ, DeYoung L, Brock GB, Sims SM |
| Source: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY Volume: 288 Issue: 3 Pages: C650-C658 Published: MAR 2005 |
| Times Cited: 17 References: 36 |
| Abstract: Tonic contraction of corpus cavernosum smooth muscle cells (SMCs) maintains the flaccid state of the penis, and relaxation is initiated by nitric oxide ( NO), leading to erection. Our aim was to investigate the effect of NO on the smooth muscle cellular response to adrenergic stimulation in corpus cavernosum. Fura-2 fluorescence was used to record intracellular Ca2+ concentration ([Ca2+](i)) from freshly isolated SMCs from rat and human. Phenylephrine ( PE) transiently elevated [Ca2+](i) in the presence and absence of extracellular Ca2+, indicating release from intracellular stores. Whereas the NO donor S-nitroso-N-acetylpenicillamine ( SNAP) with sildenafil citrate (SIL) caused no change in basal [Ca2+](i), the PE-induced rise of [Ca2+](i) was reversibly inhibited by 27 +/- 7% ( n = 21, P < 0.005) in rat and by 55 +/- 15% ( n = 9, P < 0.01) in human SMCs. SNAP and SIL also reduced the contractile response to PE. To investigate the mechanism, we applied mediators alone or in combination. The soluble guanylyl cyclase inhibitor ODQ reduced the effect of SNAP and SIL. SIL, cGMP analogs, and NO donors without SIL did not reduce the PE-induced rise of [Ca2+](i). However, the combination of 8-bromo-cGMP with SNAP reduced the Ca2+ peak by 42 +/- 9% ( n = 22, P < 0.01). Our results demonstrate that NO and cGMP act synergistically to reduce Ca2+ release from intracellular stores. Reduction of intracellular Ca2+ release may contribute to relaxation of the corpus cavernosum, leading to erection. |
| Document Type: Article |
| Language: English |
| Reprint Address: Williams, BA (reprint author), Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 5C1 Canada |
Addresses:
1. Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 5C1 Canada
2. Univ Western Ontario, Dept Surg, London, ON N6A 3K7 Canada
3. Lawson Hlth Res Inst, London, ON Canada |
| Publisher: AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Cell Biology; Physiology |
| IDS Number: 894ME |
| ISSN: 0363-6143 |
| DOI: 10.1152/ajpcell.00475.2004 |
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