Hansjörg Teschemacher

Opioid activities of β-casomorphins

Abstract β-Casomorphin-7 (H-Tyr-Pro-Phe-Pro-Gly-Pro-Ile-OH) and its analogues: β-casomorphin-6, (-5) and (-4) (derived by sequential removal of respectively one, two or three amino acid residues from the C-terminus), were tested for their opioid activities in a variety of assay systems. Each of the four peptides displayed opioid activity in an opiate receptor binding assay, the isolated mouse vas deferens (MVD), the guinea-pig ileum longitudinal muscle myenteric plexus preparation (GPI) and produced naloxone-reversible analgesia after intracerebroventricular injection into rats. In contrast, none of the peptides displayed opioid activity in the isolated rat vas deferens preparation (RVD). β-Casomorphin-5 was the most potent compound in all the assays employed. Each β-casomorphin was more potent on the GPI than on the MVD. In view of the fact that the GPI, MVD and RVD are populated predominantly by μ-, δ- and e-receptors, respectively, the β-casomorphins probably represent μ-type opiate receptor agonists.

Intracerebral distribution pattern of radioactive morphine and morphine-like drugs after intraventricular and intrathecal injection

SummaryThe intracerebral distribution patterns of 14C-morphine, 3H-dihydromorphine, and 3H-fentanyl after intraventricular injection were studied autoradiographically in rats and rabbits. The extent of permeation into the ventricular wall was measured at different times after injection. The hydrophilic morphine and dihydromorphine could be demonstrated within the tissue up to 4 hours. They seemed to be retained within the gray matter and hindered in crossing fiber bundles. On the other hand, the lipophilic fentanyl was quickly removed from the brain but remained relatively longer demonstrable within the white matter. Also, after intrathecal injection of 14C-morphine a time dependent spread from the injection site was observed. The use of autoradiography in pharmacological experiments as described was found advantageous. Thus, it is possible to correlate directly, the time course of the pharmacological effect and the respective distribution pattern of the drug applied. This may lead to better information about the probable sites of drug action.

Opioid Peptides..: Immunological Significance?

During the last decade information has been collected from numerous studies about the biosynthesis, structure, distribution, and effects of endogenous opioid peptides; however, our knowledge about the physiological significance of these peptides is still limited. Recently, a number of in vitro findings have shown that opioid peptides might play an immunological role under in vivo conditions. In these studies, opioid peptides have been shown to elicit various effects on cells of the immune system; however, the integration of these effects into the network of interactions between immune and neuroendocrine systems has not drawn much interest so far. Moreover, how far these in vitro findings have any relevance under in vivo conditions remains to be clarified. In view of these aspects a number of studies, including our own contributions to this field, are reviewed in this article.

CENTRAL NICOTINE‐AND MUSCARINELIKE PROPERTIES OF CHOLINOMIMETIC DRUGS WITH REGARD TO THEIR LIPID SOLUBILITIES

The classical differentiation and definition of muscarineand nicotine-like effects of choline esters by Dale, “a ‘muscarine’ action paralysed by atropine and a ‘nicotine’ action paralysed by excess of nicotine,” related exclusively to peripheral effects. Pfeiffer and Jenny (1954) expanded the definition “muscarinelike” and “nicotinelike” to the central nervous system (CNS). On first view, this had a somewhat surprising aspect: The central nicotinic actions corresponding to the nicotinic action upon peripheral ganglia were less clearly definable than the central muscarinic actions, which were supposed to correspond to actions upon the terminals of the parasympathetic nervous system, but not to the peripheral ganglia. The presumptive contradiction was elucidated by further investigations showing that cholinomimetics have also a muscarinic action, (i,e., an action which is abolished by small doses of atropine) upon the ganglia of the peripheral nervous system (c.f. Volle, 1965). The identification of “ganglionic stimulation” with “nicotinelike action,” often still made, is therefore not justified at present. The useful differentiation between nicotineand muscarine-like effects upon the CNS has also been supported by investigations of the effect of substances upon single nerve cells by means of microelectrophoresis. Recent results even indicate that both types of receptors seem occasionally to be present at the same nerve cell (Curtis & Ryall, 1964). The concept of a fundamental uniformity of muscarinic receptors in the CNS and in the periphery was the basis for our investigations in which central and peripheral effects of cholinomimetics and cholinolytics were compared. From the ratio of central to peripheral activity, the degree of occupation of receptors in the CNS and in the periphery was estimated. The question then arose whether correlation could be found between the lipid s o h bilities of the substances-an important parameter for their ability to penetrate into the CNS-and the ratio of central to peripheral activity (Herz et d. 1965, 1966). In studying cholinomimetics it was necessary to distinguish between their nicotinic and their muscarinic effects. This paper will constitute a short review of these investigations, especially as they concern the separation of central muscarinic and nicotinic effects.

Interaction of human β-endorphin with the terminal SC5b-9 and “preterminal” SC5b-7 and SC5b-8 complexes of human complement

Human beta-endorphin (beta H-EP) is demonstrated to bind to the preterminal SC5b-7 and SC5b-8 complexes and to the terminal SC5b-9 complex of human complement. Detailed binding studies revealed saturability, reversibility and structural specificity of the beta H-EP interaction with high or low affinity non-opiate binding sites on SC5b-7 and SC5b-9 complexes. The high affinity binding sites seem to be located predominantly on C5b, C6 or C7 subunits of the complexes.

Endogenous opioids: cold-induced release from pituitary tissue in vitro; extraction from pituitary and milk

All endogenous opioids identified so far are peptides—‘endorphins’. Recently, however, endogenous opioids which might belong to another class of compounds have been detected in the blood. Both classes of endogenous opioids have been studied in this investigation. Pituitary opioid peptides were released from anterior lobe tissue on incubation between 0 and 15 °C, as reported for most of the pituitary hormones. β-endorphin and a and/or γ-endorphin were found in the incubation media. Using a hot glacial acetic acid extraction method, besides β-endorphin, an opioid with properties similar to those of the opioids detected in blood was extracted from bovine posterior pituitary lobes. To this class of endogenous opioids, apparently, also belongs a substance extracted from bovine and human milk.

Reanimation von Patienten mit Kreislaufstillstand am Computer

Kein Zweifel — der Einsatz von Computern auf dem Sektor Medizin nimmt rapide zu: Das Angebot an Expertensystemen, Datenbanken, Krankenhaus-Organisationssystemen, Arzneimittel-Therapiesystemen, computergestutzten Diagnose- und Behandlungsverfahren in der Fachpresse oder auf Ausstellungen (MEDICA, 1991) signalisiert es. Insbesondere in den Arztpraxen setzt sich die EDV durch (Mohr, 1990; 1991) — gelegentlich noch kritisch beleuchtet (Schafer, 1992). Offenbar gibt es hier einen “Markt”, d.h. eine finanziell gestutzte Nachfrage des Verbrauchers oder Nutzers aufgrund einer gewinnversprechenden Kosten-Nutzen-Analyse. Demgegenuber nimmt sich die Zuwachsrate an computergestutzten Unterrichtsverfahren in der Arzteausbildung — ubrigens auch im Vergleich zu anderen Landern, etwa USA oder Canada — eher bescheiden aus. Woran liegt dies?

Endogenous ligands of opiate receptors

SummaryFrom brain and from pituitary tissue of vertebrates several peptides —with molecular weights between 500 and 3500 daltons — have been isolated, which behave like opiates in opiate receptor binding assays, in isolated tissue preparations and in the intact animal.