Abstract

1. To continue the investigation into the physiological roles of the endogenous opioid peptides, methionine-enkephalin, leucine-enkephalin and beta-endorphin. 2. To continue with the characterization of the binding of opiates and opioid peptides to mu-, delta- and kappa-receptor sites. To search for agonists and antagonists which interact specifically with each type of these receptors. 3. To use specific agonists or antagonists for the study of the differential distribution of the various opiate receptors in the central and peripheral nervous system of various species. 4. To continue to study the mechanisms mediating the release of the enkephalins and to examine the differences in the release of methionine-and leucine-enkephalin. To investigate the modulation of release by drugs. 5. To study the biosynthesis of the two enkephalins and, in particular, the kinetics of the interactions between the enkephalins and their putative precursors. 6. To continue to assess the agonist and antagonist characteristics of new synthetic narcotic analgesic drugs and to pay special attention to their differential interactions with the mu, delta, and kappa-receptors. 7. To continue the investigation of the role of the interaction between the endogenous opioid peptides and exogenously applied narcotic analgesics in the development of tolerance and dependence.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA000662-10
Application #
3206808
Study Section
Pharmacology I Research Subcommittee (DABR)
Project Start
1973-06-01
Project End
1986-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Aberdeen
Department
Type
DUNS #
212381045
City
Aberdeen
State
Country
United Kingdom
Zip Code
AB24 3FX

  Publications

Hughes, J; Kosterlitz, H W; Smith, T W (1997) The distribution of methionine-enkephalin and leucine-enkephalin in the brain and peripheral tissues. 1977. Br J Pharmacol 120:428-36; discussion 426-7
Sagan, S; Corbett, A D; Amiche, M et al. (1991) Opioid activity of dermenkephalin analogues in the guinea-pig myenteric plexus and the hamster vas deferens. Br J Pharmacol 104:428-32
Corbett, A D; Gillan, M G; Kosterlitz, H W (1991) Electrically-induced release of opioid peptides from the guinea-pig myenteric plexus preparation. J Recept Res 11:665-73
Paterson, S J; Robson, L E; Kosterlitz, H W et al. (1990) Effect of Tris, HEPES, and TES buffers on binding at mu-, delta-, and kappa-opioid sites in guinea pig brain. J Pharmacol Methods 23:275-83
Kosterlitz, H W; Corbett, A D; Paterson, S J (1989) Opioid receptors and ligands. NIDA Res Monogr 95:159-66
Petrillo, P; La Regina, A; Sbacchi, M et al. (1989) Regional variations in binding capacities at mu-, delta- and kappa-opioid sites in membrane suspensions from rabbit brain. Eur J Pharmacol 166:213-7
Kosterlitz, H W; Paterson, S J; Robson, L E (1988) Modulation of binding at opioid receptors by mono- and divalent cations and by cholinergic compounds. J Recept Res 8:363-73
Corbett, A D; McKnight, A T; Kosterlitz, H W (1988) Tissue content of opioid peptides in the myenteric plexus-longitudinal muscle of guinea-pig small intestine. J Neurochem 51:32-7
Kosterlitz, H W; Paterson, S J; Robson, L E et al. (1987) Effects of cations on binding, in membrane suspensions, of various opioids at mu-sites of rabbit cerebellum and kappa-sites of guinea-pig cerebellum. Br J Pharmacol 91:431-7
Traynor, J R; Corbett, A D; Kosterlitz, H W (1987) Diprenorphine has agonist activity at opioid kappa-receptors in the myenteric plexus of the guinea-pig ileum. Eur J Pharmacol 137:85-9

Showing the most recent 10 out of 25 publications