Nonopioid effects of beta-casomorphin-5 in guinea pig heart: alterations to the beta-adrenoceptor-G-protein complex and inhibition of myocardial responses to isoproterenol.
The influence of beta-casomorphin-5 on the beta-adrenoceptor complex in guinea pig heart membranes was studied by means of binding studies, G-protein investigations and isolated heart preparations. In nanomolar concentrations beta-CM-5 induced an increase in receptor affinity towards the agonist isoproterenol whereas the antagonist affinity was reduced. The isoproterenol-stimulated increase in cardiac contractility, moreover, is reduced by 10 nM beta-CM-5. Furthermore, beta-CM-5 was found to inhibit the isoproterenol-induced GDP/GTP exchange as well as the [35S]GTP[S] binding to guinea pig heart membranes, indicating an involvement of G-proteins. These findings suggest that low concentrations of beta-CM-5 modulate the functional properties of the myocardial beta-adrenoceptor-G-protein complex, presumably resulting in its desensitization. The observed effects of beta-CM-5 are not prevented by naloxone and, therefore, are nonopioid in nature.
Liebmann
C
C
Institute of Biochemistry and Biophysics, Biological and Pharmaceutical Faculty, Friedrich-Schiller-University, FRG, Jena.
Mentz
P
P
Schnittler
M
M
Schrader
U
U
Neubert
K
K
Barth
A
A
D000595:Amino Acid Sequence; D000818:Animals; D004723:Endorphins / Q000737:chemistry / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D004723:Endorphins; D010446:Peptide Fragments; D011943:Receptors, Adrenergic, beta; C034812:beta-casomorphin 5; D019204:GTP-Binding Proteins; D007545:Isoproterenol