title: Mechanisms mediating the antiproliferative effects of nitric oxide in cultured human airway smooth muscle cells.
abstract: We have characterised the mechanisms involved in the antiproliferative effect of NO in human airway smooth muscle cells (HASMC). S-Nitroso-N-acetyl penicillamine, a nitric oxide donor, inhibited proliferation in both G(1) and S phases of the cell cycle. Additionally, experiments with 8-bromo-cGMP, haemoglobin, a NO scavenger and zaprinast, a cGMP-specific phosphodiesterase inhibitor, showed that both effects were NO-mediated. The G(1) phase inhibition was cGMP-dependent whereas the S phase inhibition was due to a cGMP-independent inhibition of ribonucleotide reductase. These results demonstrate that NO inhibits HASMC proliferation by cGMP-dependent and -independent mechanisms acting at distinct points in the cell cycle.
authors.affiliation: Department of Respiratory Medicine, Al-Mansourah University Hospital, Egypt.
authors.forename: A M
authors.initials: AM
authors.lastname: Hamad
authors.forename: A J
authors.initials: AJ
authors.lastname: Knox
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003839:Deoxyadenosines / Q000494:pharmacology; D003849:Deoxyguanosine / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D006801:Humans; D008751:Methylene Blue / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
chemical_list: D016895:Culture Media, Serum-Free; D003839:Deoxyadenosines; D006454:Hemoglobins; D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D003849:Deoxyguanosine; C011145:zaprinast; D008751:Methylene Blue; D013936:Thymidine