Forskolin

10: Ann Thorac Surg 2002 Oct;74(4):1213-8

Potent adenylate cyclase agonist forskolin restores myoprotective effects of ischemic preconditioning in rat hearts after myocardial infarction.

Mieno S, Horimoto H, Watanabe F, Nakai Y, Furuya E, Sasaki S.

Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Takatsuki, Japan.

BACKGROUND: The purpose of this study was to determine whether ischemic preconditioning (IPC) provides myoprotective effects in post-myocardial infarction (MI) hearts, and whether beta adrenergic signaling is involved in IPC. METHODS: Rats were subjected to either ligation of the left anterior descending coronary artery (LAD) resulting in MI, or a sham operation. Two weeks later, hearts were isolated and perfused. Six groups (n = 7 each) were studied: group 1, control (sham operation); group 2, sham operation + IPC; group 3, post-MI; group 4, post-MI + IPC; group 5, post-MI + forskolin; group 6, post-MI + forskolin + IPC. IPC consisted of two cycles of 5 minutes of global ischemia. The adenylate cyclase agonist forskolin (1.0 x 10(-5) M) was administered in post-MI hearts either alone (group 5) or for 5 minutes before IPC (group 6). All hearts were then subjected to 20 minutes of global ischemia followed by 120 minutes of reperfusion, after which infarct size was measured. Concentrations of endogenous catecholamines and myocardial mRNA expression of beta 2 adrenergic receptor were measured in the post-MI model. RESULTS: (1) IPC reduced infarct size in shams, from 34.7 +/- 5.2% in group 1 to 21.4 +/- 3.8% in group 2, but did not affect infarct size in post-MI hearts (group 3 versus group 4). (2) Forskolin combined with IPC reduced infarct size in post-MI hearts to 29.3 +/- 3.4% (group 6), but not in group 5 where the value was 39.3 +/- 4.8%. (3) Beta 2 adrenergic receptor mRNA expression in post-MI hearts was significantly decreased as compared with sham-operated animals. CONCLUSIONS: The results indicate that downregulation of beta adrenergic receptors in post-MI hearts may be associated with ineffectiveness of IPC, and that beta adrenergic signaling, especially in relation to adenylate cyclase activation, may be required to generate the IPC response in post-MI hearts.

PMID: 12400771

[top]


4mg noneto biocompare formulae omd ToxicPlants DictCellBio MolBioDict ( test position ) BioChemical Suppliers

A23187	Actinomycin	Aflatoxin	Anisomycin	Aphidicolin	Ascomycin
Bleomycin	Brefeldin	Cerulenin	Chromomycin	Geldanamycin	Cyclopiazonic acid
Cytochalasin	Forskolin	Fumagillin	Fumonisin	Hypericin	K252a
KT5823	Mitomycin	Nigericin	Ochratoxin	Oligomycin	Mycophenolic acid
Paclitaxel	Patulin	Paxilline	Penitrem	Puromycin	Penicillic acid
Radicicol	Rapamycin	Staurosporine	Sterigmatocystin	Thapsigargin	Tunicamycin
Verruculogen	Wortmannin