Role of Endogenous Opioids in Central Cardiovascular Regulation and Dysregulation

Faden, Alan I.

doi:10.1007/978-3-642-77540-6_8

Cited by 7 publications

(4 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Parameters for the absorption kinet ics obtained following s.c. administration of morphine suggested that naloxone facilitated the absorption of mor phine from the injected site (decreased MAT and in creased F). It is well known that opioid agonists (especial ly in a high dose range) modify cardiovascular functions, and there are several reports that naloxone is useful for treating cardiovascular deficiency (19,20). Naloxone decreased the morphine concentration after a large dose of morphine, but not after a small dose of morphine.…”

Section: Discussionmentioning

confidence: 97%

Effect of Naloxone on the Morphine Concentration in the Central Nervous System and Plasma in Rats

Miyamoto¹,

Morita²,

Nakamura³

et al. 1993

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-We investigated whether the distribution (concentration) of morphine in the central nervous system (CNS) after systemic administration could be an index for the in vivo binding of morphine. Neither the morphine concentration nor its decline correlated with the density of opiate receptors. Naloxone de creased the morphine concentration in some CNS regions and plasma after a high dose of morphine, but not after a small dose of morphine. The CNS regions in which naloxone decreased the morphine concentration did not correlate with the density of opiate receptors, and the concentration ratios (CNS regions versus plasma) of morphine were not affected by naloxone. These results suggested that the morphine concentra tion in the CNS did not reflect the in vivo binding of morphine and that the naloxone-induced decrease in morphine concentration was not due to a displacement of morphine from its receptor sites but due to a change in morphine kinetics. Pharmacokinetic studies suggested that naloxone decreased the morphine con centration through an increased volume of morphine distribution. This naloxone-induced decrease in mor phine concentration may contribute to the naloxone-induced inhibition of morphine action in addition to the competitive antagonism at opiate receptors.

show abstract

Section: Discussionmentioning

confidence: 97%

Effect of Naloxone on the Morphine Concentration in the Central Nervous System and Plasma in Rats

Miyamoto¹,

Morita²,

Nakamura³

et al. 1993

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…Opioids are known to produce their pharmacological actions on p, S and kappa receptors, but the role of each type of opioid receptor in hypertension is unclear. Generally, the stimulation of p opioid receptors have been shown to be responsible for increased blood pressure and stimulation of kappa opioid receptors inducing cardiodepression [25]. Chronic administration of naloxone was used to upregulate opioid receptors resulting in an enhanced cardiovascular depressant response to morphine [26].…”

Section: Discussionmentioning

confidence: 99%

³H-Naloxone Binding in Brain Regions of Normotensive Wistar, Spontaneously Hypertensive and Renal Hypertensive Rats

1994

View full text Add to dashboard Cite

In order to study the role of opioid receptors in two models of experimental hypertension the binding of 3H-naloxone to membranes prepared from discrete brain regions and spinal cord was determined. Renal hypertensive rats (RHR) were found to have a greater density of 3H-naloxone binding sites in the hippocampus and hypothalamus when compared to spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NR). The apparent dissociation constant (Kd) for 3H-naloxone binding did not differ between groups.

show abstract

“…Previous studies investigating the cardiovascular effects of opioid receptor agonists in the intact animal (for review see Faden 1993), isolated perfused hearts (Clô et al 1985;Ventura et al 1987), or muscle strip preparations (Goldberg and Padget 1969) have yielded conflicting results regarding the inotropic effects. These studies cannot distinguish between opioid effects on cardiomyocytes or other cardiac targets, e.g.…”

Section: Discussionmentioning

confidence: 99%

“…It has long been recognized that opiates and opioid peptides have potent actions on the cardiovascular system (for reviews see Holaday 1983;Feuerstein and Sirén 1987;Faden, 1993). Alterations in heart rate and blood pressure due to their action on the central nervous system have been described.…”

Section: Introductionmentioning

confidence: 99%

Diminution of contractile response by κ-opioid receptor agonists in isolated rat ventricular cardiomyocytes is mediated via a pertussis toxin-sensitive G protein

Wenzlaff

Stein

Teschemacher

1998

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Opioids directly decrease the contractile response of isolated ventricular cardiomyocytes to electrical stimulation. To investigate whether these effects are mediated via GTP-binding G(i/o) proteins we examined the influence of pertussis toxin on the effects of the kappa-opioid receptor agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benz eneacetamide (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 microM (U-50,488) and 1 microM [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 G(i/o) proteins. In addition, the non-selective opioid receptor antagonist (-)-naloxone and the kappa-opioid receptor antagonist nor-binaltorphimine antagonized the effects of U-50,488 and dynorphin A (1-8) on the contractile response. Furthermore, the mu- and delta-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 kappa-opioid receptors. The direct effect of kappa-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.

show abstract

Role of Endogenous Opioids in Central Cardiovascular Regulation and Dysregulation

Cited by 7 publications

References 76 publications

Effect of Naloxone on the Morphine Concentration in the Central Nervous System and Plasma in Rats

Effect of Naloxone on the Morphine Concentration in the Central Nervous System and Plasma in Rats

³H-Naloxone Binding in Brain Regions of Normotensive Wistar, Spontaneously Hypertensive and Renal Hypertensive Rats

Diminution of contractile response by κ-opioid receptor agonists in isolated rat ventricular cardiomyocytes is mediated via a pertussis toxin-sensitive G protein

Contact Info

Product

Resources

About

Role of Endogenous Opioids in Central Cardiovascular Regulation and Dysregulation

Cited by 7 publications

References 76 publications

Effect of Naloxone on the Morphine Concentration in the Central Nervous System and Plasma in Rats

Effect of Naloxone on the Morphine Concentration in the Central Nervous System and Plasma in Rats

3H-Naloxone Binding in Brain Regions of Normotensive Wistar, Spontaneously Hypertensive and Renal Hypertensive Rats

Diminution of contractile response by κ-opioid receptor agonists in isolated rat ventricular cardiomyocytes is mediated via a pertussis toxin-sensitive G protein

Contact Info

Product

Resources

About

³H-Naloxone Binding in Brain Regions of Normotensive Wistar, Spontaneously Hypertensive and Renal Hypertensive Rats