Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-2-4
pubmed:abstractText
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 Ca(2+) concentration ([Ca(2+)](i)) from freshly isolated SMCs from rat and human. Phenylephrine (PE) transiently elevated [Ca(2+)](i) in the presence and absence of extracellular Ca(2+), indicating release from intracellular stores. Whereas the NO donor S-nitroso-N-acetylpenicillamine (SNAP) with sildenafil citrate (SIL) caused no change in basal [Ca(2+)](i), the PE-induced rise of [Ca(2+)](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 [Ca(2+)](i). However, the combination of 8-bromo-cGMP with SNAP reduced the Ca(2+) peak by 42 +/- 9% (n = 22, P < 0.01). Our results demonstrate that NO and cGMP act synergistically to reduce Ca(2+) release from intracellular stores. Reduction of intracellular Ca(2+) release may contribute to relaxation of the corpus cavernosum, leading to erection.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0363-6143
pubmed:author
pubmed:issnType
Print
pubmed:volume
288
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C650-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15537706-3',5'-Cyclic-GMP Phosphodiesterases, pubmed-meshheading:15537706-Animals, pubmed-meshheading:15537706-Calcium, pubmed-meshheading:15537706-Calcium Signaling, pubmed-meshheading:15537706-Cells, Cultured, pubmed-meshheading:15537706-Cyclic GMP, pubmed-meshheading:15537706-Fluorescent Dyes, pubmed-meshheading:15537706-Fura-2, pubmed-meshheading:15537706-Humans, pubmed-meshheading:15537706-Male, pubmed-meshheading:15537706-Muscle, Smooth, pubmed-meshheading:15537706-Muscle Contraction, pubmed-meshheading:15537706-Nitric Oxide, pubmed-meshheading:15537706-Nitric Oxide Donors, pubmed-meshheading:15537706-Penis, pubmed-meshheading:15537706-Piperazines, pubmed-meshheading:15537706-Purines, pubmed-meshheading:15537706-Rats, pubmed-meshheading:15537706-Rats, Sprague-Dawley, pubmed-meshheading:15537706-Sulfones, pubmed-meshheading:15537706-Vasodilator Agents
pubmed:year
2005
pubmed:articleTitle
Regulation of intracellular Ca2+ release in corpus cavernosum smooth muscle: synergism between nitric oxide and cGMP.
pubmed:affiliation
Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada N6A 5C1. bwilli8@uwo.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't