PubMed Health⌕ Search

Biomedical subjects

M Wüster

Publications and source records attributed to M Wüster.

52 records · Page 3Linked to original sources
PubMed1980

Some aspects of opiate receptors.

There is accumulating evidence that the existence of various endorphins is parallelled by the existence of multiple opiate receptors for these different ligands. At present, it appears that opiate binding sites in the mouse vas deferens are specifically sensitive to enkephalins, while the receptors of the vas deferens of the rat are selectively sensitive to beta-endorphin. Although enkephalin is present in the guinea pig ileum, it is not yet known if there are other endogenous ligands that preferentially combine with the mu-receptors located in this tissue. We suggest that a preference of the particular opiate receptors for specific ligands with different properties (e.g., their different susceptibility to enzymatic degradation) could characterize these binding sites as receptors for either neurotransmitters or hormones.

Animals↗
PubMed1979

Rapid changes in enkephalin levels in rat striatum and hypothalamus induced by diazepam.

The acute treatment of rats with diazepam induces pronounced changes in brain enkephalin concentrations, as was estimated for methionine(met)-enkephalin and in some representative experiments for leucine(leu)-enkephalin, employing highly specific radioimmunoassays. Diazepam selectively increased the enkephalin concentrations in the hypothalamus by about 35%, and lowered it in the corpus striatum by roughly 25%; no changes could be detected in the medulla oblongata/pons or midbrain. The drug-induced changes displayed a rapid onset. Peak effects were reached by 2 to 5 min after injection. Changes observed in the hypothalamus were only short lasting and were apparently parallelled by diazepam concentrations in the brain, whereas the decrease in the striatum was of markedly longer duration. Presently, the mechanism underlying all these changes is unknown. Whereas an increase in enkephalin concentrations in the hypothalamus may be discussed in terms of the anti-stress effect of benzodiazepines, the observed drop in striatal enkephalin is not obviously to be correlated to behavioural changes induced by these drugs.

Animals↗
PubMed1979

Centrally and peripherally mediated inhibition of intestinal motility by opioids.

Intracerebroventricularly injected morphine is 50-fold more potent in arresting intestinal peristalsis in rats, mice or guinea pigs than morphine administered systemically. Using quaternary naloxone as narcotic antagonist, it has been demonstrated that the peripheral pathway of the centrally mediated constipatory effect of morphine does not involve opioid peptidergic mechanisms. Further, this effect is not due to the release of opioid peptides from the pituitary, since hypophysectomy fails to affect the antipropulsive activity of morphine. On the other hand, the intestinal motility can be affected directly by activation of opiate receptors located in the gut. This was best demonstrated with loperamide, which exhibits predominantly a peripheral site of action. Thus, two mechanisms of the action of morphine on gastrointestinal propulsive activity have been demonstrated. One arises in the central nervous system (CNS) and is mediated peripherally not by opioid peptidergic pathways, whereas the other is due to a direct action of morphine on the gut.

Animals↗
PubMed1979

Supersensitivity to opioids following the chronic blockade of endorphin action by naloxone.

Chronic treatment of guinea pigs with the narcotic antagonist naloxone (pellet implantation technique) caused an increased sensitivity to opioids of the electrically stimulated longitudinal muscle-myenteric plexus preparation of the ileum. This supersensitivity is associated with an elevation of the total number of opiate receptor binding sites in both the peripheral and the central nervous system.

Animals↗
PubMed1979

Specificity of opioids towards the mu-, delta- and epsilon-opiate receptors.

The potency of a number of opioid agonists have been determined on three different bioassays, the isolated guinea-pig ileum (GPI), the mouse vas deferens (MVD) and the rat vas deferens (RVD). With the exception of beta-endorphin, compounds with opioid activity on the GPI and the MVD exhibited considerably less or no activity on the RVD; the opiate receptor in this latter tissue being thus characterized as beta-endorphin selective ('epsilon-receptor'). A system of classification of opioids according to their relative relative affinities for particular opiate receptor types is given.

Animals↗
PubMed1978

The opiate-like action of tilidine is mediated by metabolites.

The analgesic effect of tilidine in rats is completely antagonized by the narcotic antagonist naloxone. Radioreceptor assays revealed, however, that the main metabolites of tilidine, nortilidine and bisnortilidine, rather than tilidine exhibit affinity to opiate receptors. These findings were confirmed in studies using the electrically stimulated guinea pig ileum and the mouse vas deferens. Chronic tilidine administration to rats caused a considerable degree of physical dependence, which was expected from the ability of the intact animal to metabolize tilidine. In the isolated ileum from chronically morphinized guinea pigs, both nortilidine and bisnortilidine fully substituted for morphine in preventing induction of withdrawal, indicating dependence liability of these metabolites.

Analgesia↗
PubMedDate not supplied

The development of opiate tolerance may dissociate from dependence.

Experiments on opiate sensitive peripheral tissue preparations such as the mouse vas deferens and the guinea-pig ileum have demonstrated the ability to induce very high degrees of selective tolerance towards particular opiate agonists. Interestingly, the highly tolerant mouse vas deferens failed to display any sign of dependence as judged by the inability of naloxone to precipitate a withdrawal sign. In analogy, the present studies on the guinea-pig ileum revealed a striking dissociation in the degree of tolerance and dependence developed. Opiate receptor binding studies on both tissues point to distinct differences in the opiate-induced effector mechanisms. It is concluded that adaptational changes upon chronic opiate receptor activation may occur at multiple sites within the effector system of the opiate receptor.

Animals↗
PubMedDate not supplied

Endogenous ligands for kappa-opiate receptors.

The receptor preferences of opioids in the mouse vas deferens was tested by means of tolerance and cross-tolerance studies. The preparations were rendered tolerant in situ by superfusion with the kappa-receptor agonist dynorphin and with alpha-neoendorphin, respectively, and set up in vitro in the presence of the respective peptide to maintain tolerance. The investigations revealed strong kappa-agonistic activities both of alpha-neoendorphin and of dynorphin and its fragments 1-13 and 1-11. As the dynorphin chain shortened, the kappa-receptor activity declined and delta-receptor activity became progressively apparent. Interestingly, the octapeptide met-enkephalin[Arg6,Gly7,Leu8], a fragment of the adrenal medulla proenkephalin, also displayed considerable kappa-agonistic properties under the experimental conditions employed. Presumably, the decapeptide alpha-neoendorphin and the octapeptide met-enkephalin[Arg6,Gly7,Leu8] cover in addition to the kappa-receptor population in the MVD further opiate receptors, most probably delta-receptors.

Animals↗