Effect of hemin and carbon monoxide releasing molecule (CORM-3) on cGMP in rat penile tissue.
BACKGROUND
Cyclic guanosine monophosphate (cGMP) levels can be regulated by heme oxygenase-1 and 2 (HO-1 and HO-2)-derived carbon monoxide (CO).


OBJECTIVE
Assessment of the effect of upregulating CO in rat corpora cavernosa (CC) on cavernous cGMP.


METHODS
Three experimental groups were studied: first group (N = 40), short-term HO induction over 2 weeks by injection of intraperitoneal increasing doses of hemin; the second group (N = 40) was subjected to intracavernosal injection of CO donor, CORM-3, or its inactive form (iCORM-3) over 2 weeks; the third group (N = 60) was subdivided into three subgroups: the first one received a combined hemin and CORM-3, the second one received hemin and its inhibitor stannus mesoporphyrin (SnMP), and third one received a combined hemin, CORM-3, and SnMP.


METHODS
In CC, HO-1 and HO-2 gene expression, Northern blot and Western blot, cGMP levels, and HO enzyme activity.


RESULTS
In the first group, maximum induction of HO-1 gene expression, HO enzyme activity, and cGMP occurred with 4-mg hemin dose with a successive increase over 2 weeks. In the second group, CORM-3 increased cGMP by twofold compared with iCORM-3, and also increased HO-1 protein. In the third group, SnMP inhibited the enhancing effect of CORM-3 and HO on erectile signaling molecules; i.e., HO-1 gene, enzyme activity, and cGMP.


CONCLUSIONS
CORM-3- or hemin-mediated CO release could increase cavernous tissue cGMP.
Abdel Aziz
M Talaat
MT
Molecular Biology Unit, Medical Biochemistry Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
El-Asmar
M Farid
MF
Mostafa
Taymour
T
Atta
Hazem
H
Fouad
Hanan H
HH
Roshdy
Nagwa K
NK
Rashed
Laila A
LA
Obaia
Eman A
EA
Sabry
Dina A
DA
Abdel Aziz
Ahmed T
AT
Drummond
George
G
Olszanecki
Rafal
R
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D011756:Diphosphates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006427:Hemin / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D008297:Male; D008652:Mesoporphyrins / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009942:Organometallic Compounds / Q000008:administration & dosage*; D010413:Penis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D011756:Diphosphates; D008652:Mesoporphyrins; D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); C031468:mesoporphyrin IX; D006427:Hemin; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D006152:Cyclic GMP