| Abstract: |
We have developed a quantitative computerized subtraction technique to demonstrate in rat brain the regional distribution of μ1 sites, a common very-high affinity binding site for both morphine and the enkephalins. Low concentrations of [D-Ala2, D-Leu5]enkephalin selectively inhibit the μ1 binding of [3H]dihydromorphine, leaving μ2 sites, while low morphine concentrations eliminate the μ1 binding of [3H][D-Ala2, D-Leu5]enkephalin, leaving δ sites. Thus, quantitative differences between images of sections incubated in the presence and absence of these low concentrations of unlabeled opioid represent μ1 binding sites. The regional distributions of μ1 sites labeled with [3H]dihydromorphine were quite similar to those determined by using [3H][D-Ala2, D-Leu5]enkephalin. High levels of μ1 binding were observed in the periaqueductal gray, medial thalamus, and median raphe, consistent with the previously described role of μ1 sites in analgesia. Other regions with high levels of μ1 binding include the nucleus accumbens, the clusters and subcallosal streak of the striatum, hypothalamus, medial habenula, and the medial septum/diagonal band region. The proportion of total specific binding corresponding to μ1 sites varied among the regions, ranging from 14% to 75% for [3H][D-Ala2, D-Leu5]enkephalin and 20% to 52% for [3H]dihydromorphine. |
| Keywords: |
unclassified drug; drug efficacy; nonhuman; pathophysiology; methodology; animal cell; animal; metabolism; pain; central nervous system; animalia; drug receptor binding; computer; image subtraction; subtraction technique; brain; hypothalamus; rat; drug derivative; binding site; binding sites; rats; radioisotope; morphine; mu opiate receptor; receptors, opioid, mu; autoradiography; pharmacokinetics; corpus striatum; opiate receptor; brain level; nervous system; computer analysis; hippocampus; delta opiate receptor; receptors, opioid, delta; thalamus; pons; leucine enkephalin; cortex; brain chemistry; amygdaloid nucleus; topical drug administration; nucleus accumbens; periaqueductal gray matter; periaqueductal gray; raphe nucleus; receptors, opioid; priority journal; article; dihydromorphine; enkephalin, leucine-2-alanine; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; enkephalin, leucine; enkephalin, leucine 2 alanine; enkephalin[2 alanine 5 leucine]; raphe nuclei; enkephalin[2 alanine 5 leucine] h 3; dihydromorphine h 3; claustrum; olfactory tract; raphe
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