Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015:2015:906039.
doi: 10.1155/2015/906039. Epub 2015 Mar 1.

The differential effects of a selective kappa-opioid receptor agonist, U50488, in guinea pig heart tissues

Chi-Feng Hung  1 , Hsin-Ju Li  2 , Hsun-Hao Chang  3 , Gon-Ann Lee  2 , Ming Jai Su  4
Affiliations

The differential effects of a selective kappa-opioid receptor agonist, U50488, in guinea pig heart tissues

Chi-Feng Hung et al. Biomed Res Int. 2015.

Abstract

The differential effects of a selective kappa- (κ-) opioid receptor agonist, U50488, were elucidated by monitoring the contraction of isolated guinea pig atrial and ventricular muscles. In electrically driven left atria, U50488 in nanomolar concentration range decreased the contractile force. Norbinaltorphimine (norBNI), a selective κ-receptor antagonist, and pertussis toxin (PTX) abolished the negative inotropic effect of U50488. In contrast, the inhibitory effect was not affected by the pretreatment of atropine or propranolol. Even though U50488 exerted a negative inotropic effect in the left atrium, it did not affect the contractile force of the right atrium and ventricles paced at 2 Hz. Similarly, the beating rate of the spontaneously beating right atrium was also unaffected by U50488. These results indicate that the activation of κ-opioid receptors can only produce negative inotropic effect in left atria via activation of PTX-sensitive G protein in guinea pigs. The absence of negative inotropic effects in right atria and ventricles suggests that there may be a greater distribution of functional κ-opioid receptors in guinea pig left atria than in right atria and ventricles, and the distribution of the receptors may be species-specific.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Effect of U50488 on the contractile force in guinea pig atria and ventricle. Sinoatrial node of right atrium was removed. Atria and ventricle were paced at 2 Hz. After equilibrium for 30 min, U50488 and norBNI were added sequentially. (a) Left atrium. (b) Right atrium. (c) Right ventricle.
Figure 2
Figure 2
The concentration-dependent effects of U50488 on contractile force of left atrium illustrated as percentage of control. Vertical lines are SE. ∗ and ∗∗ indicate P < 0.05 and P < 0.01 as compared with control (n = 5).
Figure 3
Figure 3
Representative tracings show the effect of norBNI and PTX on the effect of U50488 in left atria. (a) A norBNI (1 μmol/L) pretreated atrium. (b) An atrium from PTX-pretreated guinea pig (150 μg/kg for 24 h).
Figure 4
Figure 4
Effect of U50488 on left atria pretreated with norBNI (n = 4) and PTX (n = 5).
Figure 5
Figure 5
Negative inotropic effect of U50488 in left atria pretreated with propranolol (3 μmol/L, n = 6) or atropine (1 μmol/L, n = 5). (a) Representative traces show the effect of U50488 on the contractile force in left atria pretreated with propranolol or atropine for 20 min. (b) Concentration-dependent effects of U50488 on contractile of left atria in the presence of propranolol or atropine. Values are expressed as percentage of control. Vertical lines are SE. ∗ and ∗∗ indicate P < 0.05 and P < 0.01 as compared with control.
Figure 6
Figure 6
Effect of U50488 on spontaneously beating rate of right atria in guinea pig. Values are presented as percentages of control (n = 6).
See this image and copyright information in PMC

References

    1. Sobanski P., Krajnik M., Shaqura M., Bloch-Boguslawska E., Schäfer M., Mousa S. A. The presence of mu-, delta-, and kappa-opioid receptors in human heart tissue. Heart and Vessels. 2014;29(6):855–863. doi: 10.1007/s00380-013-0456-5. - DOI - PubMed
    1. Tanaka K., Kersten J. R., Riess M. L. Opioid-induced cardioprotection. Current Pharmaceutical Design. 2014;20(36):5696–5705. - PMC - PubMed
    1. Theisen M. M., Schlottmann S., August C., et al. Detection and distribution of opioid peptide receptors in porcine myocardial tissue. Pharmacological Research. 2014;84:45–49. doi: 10.1016/j.phrs.2014.04.008. - DOI - PubMed
    1. Lasukova T. V., Maslov L. N., Nizkodubova S. W., Gorbunov A. S., Zibulnikov S. Y. Role of intracellular calcium and cyclic nucleotides in realization of cardioprotective effects of δ 1- and κ 1-Opioid receptor agonists. Bulletin of Experimental Biology and Medicine. 2009;148(6):877–880. doi: 10.1007/s10517-010-0840-4. - DOI - PubMed
    1. Fu L.-W., Longhurst J. C. Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia. American Journal of Physiology: Heart and Circulatory Physiology. 2013;305(1):H76–H85. doi: 10.1152/ajpheart.00091.2013. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources