CHARACTERIZATION OF THE k‐SUBTYPE OF THE OPIATE RECEPTOR IN THE GUINEA‐PIG BRAIN

British Journal of Pharmacology - Tập 73 Số 4 - Trang 939-949 - 1981
H. W. Kosterlitz1, Sue Paterson1, Linda E. Robson1
1Unit for Research on Addictive Drugs, University of Aberdeen, Marischal College, Aberdeen AB9 1AS

Tóm tắt

In homogenates of guinea‐pig brain, the characteristics of the binding of [3H]‐ethylketazocine, an agonist for the putative k‐receptor, were determined by estimation of the affinity and capacity of binding, by competitive inhibition for the binding site by unlabelled ligands and by selective protection of the binding site from alkylation by phenoxybenzamine. At 25°C the maximum number of binding sites for [3H]‐ethylketazocine was about 14pmol/g fresh brain, of which about 50% were high affinity sites. In competition experiments, the high affinity binding of [3H]‐ethylketazocine to the k‐binding site was readily displaced by several k‐agonists but not by the selective μ‐ligand, D‐Ala2, MePhe4, Glyol5‐enkephalin or the selective δ‐ligand, D‐Ala2, D‐Leu5‐enkephalin. In contrast, the k‐agonists tested so far exhibit a high degree of cross‐reactivity with the μ‐binding site but somewhat less with the δ‐binding site. Similar specificities were observed in protection experiments. The approximate proportions of the three subtypes of opiate receptor in the guinea‐pig brain are 25% μ‐binding sites, 45% δ‐binding sites and 30% k‐binding sites. The endogenous opioids, Met‐enkephalin, Leu‐enkephalin and porcine β‐endorphin have only a low affinity for the k‐binding site.

Từ khóa


Tài liệu tham khảo

10.1073/pnas.77.8.4469

10.1016/0006-2952(73)90196-2

Gilbert P.E., 1976, The effects of morphine‐ and nalorphine‐like drugs in the nondependent, morphine‐dependent and cyclazocine‐dependent spinal dog, J. Pharmac. exp. Ther., 198, 66

10.1111/j.1476-5381.1980.tb08727.x

10.1016/0014-2999(80)90303-9

Hill A.V., 1910, The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves, J. Physiol., 40, IV

10.1016/0014-2999(79)90249-8

Hiller J.M., 1980, Specific, high affinity [3H]‐ethylketazocine binding in rat central nervous system: lack of evidence for k receptors, J. Pharmac exp. Ther., 214, 516

10.1111/j.1476-5381.1975.tb07430.x

10.1111/j.1476-5381.1980.tb10422.x

Kosterlitz H.W., 1978, Assessment of analogues of opioid peptides in four parallel assays, Bull. Problems Drug Dependence, 40, 139

10.1098/rspb.1980.0122

Kosterlitz H.W., 1981, Tyr‐D‐Ala‐Gly‐MePhe‐Gly‐ol is a selective ligand for the μ‐opiate binding site, Br. J. Pharmac., 73, 299 P

Kosterlitz H.W., 1980, Binding characteristics of the k‐subtype of the opiate receptor, J. Physiol., 308, 67P

Lord J.A.H., 1976, Opiates and Endogenous Opioid Peptides, 275

10.1038/267495a0

Martin W.R., 1976, The effects of morphine‐and nalorphine‐like drugs in the nondependent and morphine‐dependent chronic spinal dog, J. Pharmac. exp. Ther., 197, 517

10.1098/rspb.1979.0076

10.1016/0024-3205(80)90107-1

10.1111/j.1749-6632.1949.tb27297.x

10.1073/pnas.77.1.281

10.1111/j.1471-4159.1980.tb12483.x

Swain H.H., 1974, Evaluation of new compounds for morphine‐like physical dependence in the rhesus monkey, Bull. Problems Drug Dependence, 36, 1168

Swain H.H., 1976, Evaluation of new compounds for morphine‐like physical dependence in the rhesus monkey, Bull. Problems Drug Dependence, 38, 768

Villarreal J.E., 1972, Evaluation of new compounds for morphine‐like physical dependence in the rhesus monkey, Bull. Problems Drug Dependence, 34, 1040

Thông tin
Thông tin xuất bản

British Journal of Pharmacology

Tập 73 Số 4

939-949

Thông tin tác giả