Expression of functional delta opioid receptors in vascular smooth muscle.

Saeed, Rania; Stefano, George B.; Murga, Jose D.; Short, Timothy W.; Qi, Feng; Bilfinger, Thomas V.; Magazine, Harold I.

doi:10.3892/ijmm.6.6.673

Cited by 19 publications

(18 citation statements)

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“…These changes in circulating opioid peptide concentrations could have significant effects on both vascular and cardiac opioid receptor activation. Plasma BE could activate both cardiac DOR (31,50,52) as well as both MOR and DOR in the vasculature (43). However, results of this study did not show altered cardiac DOR function between normotensive and hypertensive groups, suggesting that chronic decreased BE did not have a significant effect on the expression or coupling of the cardiac DOR and ultimately may not have an influence on the functional outcome of the heart subjected to untreated, prolonged hypertension.…”

Section: Discussionmentioning

confidence: 91%

Hypertensive state, independent of hypertrophy, exhibits an attenuated decrease in systolic function on cardiac κ-opioid receptor stimulation

Bolte

Newman²,

Schultz³

2009

American Journal of Physiology-Heart and Circulatory Physiology

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Opioids/opiates are commonly administered to alleviate pain, unload the heart, or decrease breathlessness in patients with advanced heart failure. As such, it is important to evaluate whether the myocardial opioidergic system is altered in cardiac disease. A hamster model of spontaneous hypertension was investigated before the development of hypertension (1 mo of age) and in the hypertensive state (10 mo of age) to evaluate the effect of prolonged hypertension on myocardial opioidergic activity. Plasma beta-endorphin was decreased before the development of hypertension and in the hypertensive state (P < 0.05). There was no change in cardiac beta-endorphin content at either time point. No differences were detected in cardiac or plasma dynorphin A, Met-enkephalin, or Leu-enkephalin, or in cardiac peptide expression of kappa- or delta-opioid receptors. mu-Opioid receptor was not detected in either model. To determine how hypertension affects myocardial opioid signaling, the ex vivo work-performing heart was used to assess the cardiac response to opioid administration in healthy hearts and those subjected to chronic hypertension. Agonists selective for the kappa- and delta-opioid receptors, but not mu-opioid receptors, induced a concentration-dependent decrease in cardiac function. The decrease in left ventricular systolic pressure on administration of the kappa-opioid receptor-selective agonist, U50488H, was attenuated in hearts from hamsters subjected to chronic, untreated hypertension (P < 0.05) compared with control. These results show that peripheral and myocardial opioid expression and signaling are altered in hypertension.

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Section: Discussionmentioning

confidence: 91%

Hypertensive state, independent of hypertrophy, exhibits an attenuated decrease in systolic function on cardiac κ-opioid receptor stimulation

Bolte

Newman²,

Schultz³

2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Other non-neuronal locations where opioid binding sites and the expression of opioid receptor transcripts that have been demonstrated include: endocrine cells [20], vascular endothelial cells [21], smooth muscle [22], keratinocytes [23] and cells of the immune system, e.g., macrophages and lymphocytes through which opioid agonists modulate the vascular and immune cell functions [24]. Finally, other studies have also demonstrated that functional µ-opioid receptors are constitutively expressed in osteoblasts [25] and chondrocytes [26] and the δand κ -opioid receptors in fibroblasts [27].…”

Section: Endogenous Opioid Systemmentioning

confidence: 99%

The Involvement of the Nitric Oxide in the Effects and Expression of Opioid Receptors During Peripheral Inflammation

Pol

2007

CMC

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Peripheral inflammation enhances the antinociceptive effects of opioid receptor agonists through the activation of peripheral opioid receptors whose expression also increases during inflammatory pain. Similarly, intestinal inflammation also increases the antitransit and antiexudative effects of opioids as well as the expression of neuronal and extra-neuronal opioid receptors located in the gut. Nitric oxide has been described either as pro- or antiinflammatory and could produce both pro- and antinociceptive effects. In addition, numerous studies have shown that the L-arginine-nitric oxide-cGMP system participates in the antinociceptive and in the intestinal effects produced by opioids during peripheral inflammation by enhancing their effects. Thus, substances capable of inhibiting cyclic guanosine-3',5'-monophosphate (cGMP) degradation or nitric oxide donors increase the analgesic effects of opioid receptor agonists during peripheral inflammation. At the same time, the administration of nitric oxide synthase (NOS) or guanylate cyclase inhibitors decreases those effects. In accordance with these results, different clinical trials have also demonstrated that the co-administration of nitric oxide donors with opioids is highly beneficial in the treatment of pain in patients. In the gut, nitric oxide has a further pro- and antiinflammatory action. It is also involved in the enhanced antitransit and antiexudative effects produced by opioids and in the up-regulation of the mu-opioid receptor gene transcription observed in the inflamed intestine. To sum up, a better knowledge of the involvement of the L-arginine-nitric oxide-cGMP pathway in the opioid mechanisms of action and a better understanding of the pathways that regulate the expression of opioid receptors during peripheral inflammation are essential to developing improved analgesic/antiinflammatory therapies.

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“…Opioid receptors are found in the central and peripheral nervous system as well as in non-neuronal sites such as the vascular endothelium and immune cells (Mansour et al, 1994;Cadet et al, 2000;Saeed et al, 2000;Tomassini et al, 2003). In the gut, opioid receptors are present in the myenteric and submucosal plexuses as well as in epithelial cells (Lang et al, 1996;Bagnol et al, 1997;Pol et al, 2001) and modulate several intestinal functions such as motility and secretion under certain pathological conditions (Valle et al, 2000;Pol and Puig, 2004).…”

Section: Inflammation [D-penmentioning

confidence: 99%

Antiexudative Effects of Opioids and Expression of κ- and δ- Opioid Receptors during Intestinal Inflammation in Mice: Involvement of Nitric Oxide

Jiménez¹,

Puig²,

Pol³

2006

The Journal of Pharmacology and Experimental Therapeutics

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The study evaluates the effects of -(KOR), ␦-(DOR), and -opioid receptor (MOR) agonists on the inhibition of plasma extravasation during acute and chronic intestinal inflammation in mice. The antiexudative effects of KOR and DOR agonists in animals treated with nitric oxide synthase (NOS) inhibitors and their protein levels in the gut (whole jejunum and mucosa) and spinal cord of mice with chronic intestinal inflammation were also measured. Inflammation was induced by the intragastric administration of one (acute) or two (chronic) doses of croton oil. Plasma extravasation was measured using Evans blue and protein levels by Western blot and immunoprecipitation. Plasma extravasation was significantly increased 2.7 times during chronic inflammation. The potency of the KOR agonist trans-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolydinyl)cyclohexyl]-benzeneazetamine (U50,488H) inhibiting plasma extravasation was enhanced 26.3 times during chronic compared with acute inflammation. [D-Pen 2 ,D-Pen 5 ]-Enkephalin (DPDPE) (a DOR agonist) was also 11.8 times more potent during chronic inflammation, whereas the antiexudative effects of fentanyl (a MOR agonist) were not significantly altered. Receptor-specific antagonists reversed the effects. Protein levels of KOR and DOR in the whole jejunum and mucosa were significantly increased after chronic inflammation. Treatment with NOS inhibitors N -nitro-L-arginine methyl ester or L-N 6 -(1-iminoethyl)-lysine hydrochloride diminished plasma extravasation and inhibited the increased antiexudative effects of U50,488H and DPDPE during chronic intestinal inflammation. The data show that the enhanced antiexudative effects of KOR and DOR agonists could be related to an increased expression of KOR and DOR in the gut and that the release of nitric oxide may play a role augmenting the effects of opioids during chronic inflammation.

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Expression of functional delta opioid receptors in vascular smooth muscle.

Cited by 19 publications

References 0 publications

Hypertensive state, independent of hypertrophy, exhibits an attenuated decrease in systolic function on cardiac κ-opioid receptor stimulation

Hypertensive state, independent of hypertrophy, exhibits an attenuated decrease in systolic function on cardiac κ-opioid receptor stimulation

The Involvement of the Nitric Oxide in the Effects and Expression of Opioid Receptors During Peripheral Inflammation

Antiexudative Effects of Opioids and Expression of κ- and δ- Opioid Receptors during Intestinal Inflammation in Mice: Involvement of Nitric Oxide

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