ISSN:
1432-1912
Schlagwort(e):
Key words Cardiomyocytes
;
Opioid receptors
;
G proteins
;
Pertussis toxin
;
Dynorphin
;
U-50
;
488
;
Naloxone
;
Nor-binaltorphimine
;
DADLE
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract Opioids directly decrease the contractile response of isolated ventricular cardiomyocytes to electrical stimulation. To investigate whether these effects are mediated via GTP-binding Gi/o proteins we examined the influence of pertussis toxin on the effects of the κ-opioid receptor agonist trans-(±)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide (U-50,488) methanesulphonate and on the as yet undescribed effects of the opioid peptide dynorphin A (1–8) on contraction. In isolated, electrically driven, rat ventricular cardiomyocytes both agents concentration dependently reduced cell shortening within 15 min, decreasing the contractile response by 79±4% (n=5) and 62±2% (n=6) of control values at maximal effective concentrations of 10 µM (U-50,488) and 1 µM [dynorphin A (1–8)], respectively. Pertussis toxin pre-treatment (200 ng/ml; 4.5–5 h) completely abolished the effects of U-50,488 and dynorphin A (1–8) on the contractile response, indicating that these effects are mediated via Gi/o proteins. In addition, the non-selective opioid receptor antagonist (–)-naloxone and the κ-opioid receptor antagonist nor-binaltorphimine antagonized the effects of U-50,488 and dynorphin A (1–8) on the contractile response. Furthermore, the µ- and δ-opioid receptor agonist (D-Ala2, D-Leu5)-enkephalin (DADLE) had no effects on contraction. These results indicate that the decrease in cell shortening is due to stimulation of κ-opioid receptors. The direct effect of κ-opioid receptor agonists on the contractile response thus represents an additional mechanism for decreasing cardiac contractility, besides the M-cholinoceptor- or adenosine receptor-mediated pathway. It is conceivable that increased release of endogenous dynorphins from the heart during hypoxia may protect the heart in a similar manner to adenosine.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/PL00005265
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