Mu opiate isoreceptors: Differentiation with kappa agonists

Wood, Paul L.; Richard, Jean W.; Thakur, Mira

doi:10.1016/0024-3205(82)90145-x

Cited by 61 publications

(7 citation statements)

References 10 publications

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“…Pharmacological studies have implicated tL1 sites in a number of opiate actions, including supraspinal analgesia (12)(13)(14)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). We therefore wanted to determine if Lu sites were localized to brain regions known to be important in opiate analgesia, such as the periaqueductal gray.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, autoradiographic studies have greatly strengthened the suggestion that there are distinct ,u and 8 receptors (7)(8)(9), by demonstrating their unique regional distributions within the brain (10,11). Recently, we proposed that morphine and the enkephalins label three, not two, subpopulations of sites (12,13). In addition to the enkephalinpreferring 8 sites and the classical morphine-selective (p. 2) sites demonstrated in the guinea pig ileum (7,14), there is a common site (p.l) to which both morphine and the enkephalins bind with very high affinity.…”

mentioning

confidence: 99%

“…In addition to the enkephalinpreferring 8 sites and the classical morphine-selective (p. 2) sites demonstrated in the guinea pig ileum (7,14), there is a common site (p.l) to which both morphine and the enkephalins bind with very high affinity. This p.l site, corresponding to the high-affinity site identified in 1975 (15), differs from the pU2 and 8 sites developmentally, phylogenetically, biochemically, and pharmacologically, playing a major role in a number of important opiate actions, including supraspinal analgesia, but not in others, such as respiratory depression and most signs of physical dependence (12)(13)(14)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

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confidence: 99%

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Visualization of mu1 opiate receptors in rat brain by using a computerized autoradiographic subtraction technique.

Goodman¹,

Pasternak²

1985

Proc. Natl. Acad. Sci. U.S.A.

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We have developed a quantitative computerized subtraction technique to demonstrate in rat brain the regional distribution of #1 sites, a common very-high-affinity binding site for both morphine and the enkephalins. Autoradiography provides an effective means to accurately map opiate-binding sites within the rat brain and correlate their distribution with brain regions known to mediate opiate actions (1-6). In addition, autoradiographic studies have greatly strengthened the suggestion that there are distinct ,u and 8 receptors (7-9), by demonstrating their unique regional distributions within the brain (10,11). Recently, we proposed that morphine and the enkephalins label three, not two, subpopulations of sites (12,13). In addition to the enkephalinpreferring 8 sites and the classical morphine-selective (p.2) sites demonstrated in the guinea pig ileum (7,14), there is a common site (p.l) to which both morphine and the enkephalins bind with very high affinity. This p.l site, corresponding to the high-affinity site identified in 1975 (15), differs from the pU2 and 8 sites developmentally, phylogenetically, biochemically, and pharmacologically, playing a major role in a number of important opiate actions, including supraspinal analgesia, but not in others, such as respiratory depression and most signs of physical dependence (12)(13)(14)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34).Homogenate binding studies reveal a heterogeneous distribution of Al sites in rat brain (31, 35), but they lack the necessary detailed resolution. Autoradiography, on the other hand, faced a number of difficulties, including the lack of a ligand that could selectively label pul sites. England Nuclear) in the absence or presence of morphine sulfate (5 nM). Nonspecific binding was determined from sections incubated with the radioligand and levallorphan (1 ,uM). A section from each group was stained with hematoxylin and eosin for use in identifying anatomical regions. Slides were washed twice for 5 min each in Tris buffer (0°C), dipped once in distilled water, dried with a stream of cold dry air, placed in an x-ray film cassette along with sections containing known concentrations of tritium (dpm/mg of tissue, dry weight), exposed to LKB Ultrofilm at 4°C with desiccant for 6 months, and developed. Standards were prepared as previously described (39).The autoradiographs of the tissue sections and standards were digitized by using a Vidion-based EYECOM II image processing system linked to a PDP11/23 computer. Multiple standards on each film varied by less than 5%. The correlation of optical densities of the standards to their activity levels (dpm/mg of tissue) were fit to a polynomial equation and used to calculate the concentrations of radioligand in the tissue sections (fmol/mg of tissue). Selected regions of the experimental sections were identified on adjacent sections stained with hematoxylin and eosin. Results represent averages of values determined in two to four areas of two sections of a rat b...

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Section: Discussionmentioning

confidence: 99%

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Visualization of mu1 opiate receptors in rat brain by using a computerized autoradiographic subtraction technique.

Goodman¹,

Pasternak²

1985

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, in terms of the minimum effective doses, the k receptor agonists, es pecially bremazocine, appear to be considerably more po tent activators of PRL release than morphine. We did not use equimolar doses of the three agonists, but their molecu lar weights are not too far apart and would not explain the differences in their potencies, which also seem to be too large to be explained by differences in the affinities of the agonists for their respective receptors [22,28,29]. This ap plies especially for U-50,488 which has a lower activity for the k receptors than morphine has for the p receptors [8,29], On the other hand, the maximum elevations of PRL lev els attained following administration of the k agonists were of a moderate magnitude, not exceeding 100 ng/ml, on the average.…”

Section: Discussionmentioning

confidence: 99%

Opioid κ Receptors and the Secretion of Prolactin (PRL) and Growth Hormone (GH) in the Rat

Krulich¹,

Koenig²,

Conway³

et al. 1986

Neuroendocrinology

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The effects of bremazocine and U-50,488, two selective opioid Kreceptor agonists, and the preferential µ receptor agonist morphine on the secretion of PRL and GH were compared in conscious male rats bearing permanent right atrial cannulae for serial blood sampling and drug delivery. All three opioids stimulated PRL secretion in a dose-related manner, but the Kagonists differed from morphine in several respects. They were considerably more potent than morphine in triggering a PRL response, but were unable to elevate PRL levels to more than 100 ng/ml, whereas morphine, at the highest dose (4.5 mg/kg), induced an almost twice larger response. Also their PRL-releasing effect was inhibited more strongly by the preferential Kreceptor antagonist Mr-2266 than by naloxone, whereas Mr-2266 and naloxone, which are equipotent as antagonists of the µ receptors, were equipotent in suppressing the PRL-stimulating effect of morphine, a µ agonist. In a complete contrast to morphine, which effectively stimulated GH secretion, the Kagonists had no effect on GH release at lower doses and suppressed it at higher doses. It is concluded that the PRL-releasing effect of the Kagonists is mediated by the Kreceptors which may participate with the µ receptors in regulation of PRL secretion by opioids. The GH-inhibiting effect of the Kagonists requires further clarification.

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“…The jt-opioid partial agonist meptazinol (Stephens et al, 1978) is thought to show some selectivity (Blurton et al, 1984) between the two types of greceptor (pi and p2) which have been postulated to exist (Schultz & Wuster, 1981;Pasternak, 1982;Wood et al, 1982) and we have previously shown that the (+)-isomer of meptazinol appears to show opioid agonist activity on the guinea-pig ileum but not on the mouse vas deferens (Duchesne et al, 1984). This could also be interpreted as indicating that the p-receptors are not identical in the two tissues.…”

Section: Introductionmentioning

confidence: 99%

Similarity between μ‐opioid receptors in mouse vas deferens and guinea‐pig ileum

Goodall

Hughes

Mackay

1985

British J Pharmacology

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1 The effects ofthe opioid receptor agonist RX783006 and ofthe opioid receptor partial agonist (+ )-meptazinol have been examined on electrically-induced twitch responses of the guinea-pig isolated ileum and of the mouse isolated vas deferens.2 Loglo concentration-tissue state curves were determined for (+)-meptazinol and for RX783006, alone, in combination and, when appropriate, in the presence of naloxone (30 nM).3 Analysis of these log1o concentration-tissue state curves using the null equations derived and verified in the previous paper allows quantitation of the characteristics of the interaction of (+)-meptazinol with the opioid receptors in these tissues. 4 The results indicate that the apparent differences in the actions of (+)-meptazinol on isolated electrically-stimulated guinea-pig ileum and mouse vas deferens can be accounted for without the need to postulate differences between ji-opioid receptors in these two tissues.

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Mu opiate isoreceptors: Differentiation with kappa agonists

Cited by 61 publications

References 10 publications

Visualization of mu1 opiate receptors in rat brain by using a computerized autoradiographic subtraction technique.

Visualization of mu1 opiate receptors in rat brain by using a computerized autoradiographic subtraction technique.

Opioid κ Receptors and the Secretion of Prolactin (PRL) and Growth Hormone (GH) in the Rat

Similarity between μ‐opioid receptors in mouse vas deferens and guinea‐pig ileum

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