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Biomedical subjects

A Pfeiffer

Publications and source records attributed to A Pfeiffer.

206 records · Page 12Linked to original sources
PubMedDate not supplied

Novel and uncommon isoforms of the calcium sensing enzyme calcium/calmodulin dependent protein kinase II in heart tissue.

Calcium/calmodulin-dependent protein kinase type II (CaM kinase II) is an intracellular enzyme discovered several years ago in the brain which is obviously involved in intracellular signal transmission. Meanwhile it was detected in virtually every mammalian tissue. Several isoforms have been found to exist. Most recently the tissue distribution and the molecular structure of these isoforms have suggested that each form entails a particular function. In the present study we describe the identification, cloning, and nucleotide sequencing of two novel CaM kinase II isoforms which we discovered in rat heart. The presence of these additional subtypes makes the heart the organ which possesses the greatest number of different and unusual CaM kinase II isoforms throughout the body except for the brain. The importance of this finding is underscored by the fact that calcium is involved in the regulation of many crucial cardial parameters. The deduced amino acid sequence that we have obtained from the new CaM kinase II isoforms indicates a molecular organization which could make the design of subtype-specific inhibitory drugs for CaM kinase II possible. Such compounds would act similarly to but much more selectively than digitalis glycosides and would be likely to possess less side effects.

Amino Acid Sequence↗
PubMedDate not supplied

Different types of opiate agonists interact distinguishably with mu, delta and kappa opiate binding sites.

The present studies were undertaken to evaluate whether different types of opiate agonists interact in a distinguishable manner with mu, delta and kappa opiate binding sites. Two approaches were employed: (a) the well known effects of metal ions on opiate agonist binding affinities of subsite selective ligands were studied at mu, delta and kappa sites in rat brain homogenates. Binding parameters were obtained by simultaneous computeranalysis of displacement curves using the prototypic ligands dihydromorphine (DHM), (D-Ala2, D-Leu5) enkephalin (DADL) and ethylketocyclazocine (EKC) of the mu, delta and kappa binding sites respectively. The results show that the effects of metal ions depend not only on the binding site, but also on the ligand under investigation. (b) The interaction of the delta agonist DADL with the mu agonist DHM was investigated at mu binding sites by characterizing the type of competition occurring between the two ligands. The interaction was of the noncompetitive type. It therefore appears that the various opiate agonists either interact preferentially with different parts of a larger receptor site area or bind to topographically distinct sites on a single receptor molecule which are coupled allosterically.

Analgesics, Opioid↗
PubMedDate not supplied

Antinociceptive potencies of beta-casomorphin analogs as compared to their affinities towards mu and delta opiate receptor sites in brain and periphery.

beta-Casomorphins and their analogs were tested for their opioid activities in the myenteric plexus longitudinal muscle preparation of the guinea pig ileum (GPI), the isolated mouse vas deferens (MVD), and for their affinities to mu- delta- and kappa- binding sites in rat brain membranes. C-terminal amidation of beta-casomorphin-4 and (-5) increased opioid potency in both organ preparations (GPI, MVD) and affinity to mu-binding sites in brain whereas binding to delta-sites was diminished. These beta-casomorphin-amides displayed a 2-3 times greater naloxone reversible antinociceptive effect than natural beta-casomorphins. Introduction of D-alanine at position 2 in the beta-casomorphin-amides increased potency in the GPI whereas activity in the MVD was only slightly changed. These compounds, however, showed a remarkable increase in binding to delta-sites in brain with an unaffected or slightly increased binding to mu-sites and decreased binding to kappa-sites. D-Ala2-beta-casomorphin-4 and (-5) amides were 10 times more potent antinociceptive agents than corresponding beta-casomorphin-amides. These results suggest firstly, that peripheral delta-receptors in the MVD are not as closely related to delta-binding sites at rat brain membranes as is the case with mu-receptors in the GPI and mu-binding sites, and secondly, in addition to mu-receptors, delta-receptors may be of importance in mediating antinociception.

Animals↗
PubMedDate not supplied

Predominant involvement of mu-rather than delta- or kappa-opiate receptors in LH secretion.

Opiate alkaloids and opioid peptides have been shown to suppress plasma LH and FSH levels via a naloxone sensitive mechanism in several species including man. Three subtypes of opiate receptors have been characterized: mu, delta and kappa. The present study was designed to investigate their role in gonadotropin release. Three highly selective opioid ligands, DAGO, MRZ and DTE12 (a dimeric tetrapeptide enkephalin), were injected intraventricularly into chronically ovariectomized rats. Injection of the mu-agonist at doses of 1 and 10 nmol produced a significant suppression of LH secretion, while the delta- and kappa-agonists had no significant effect. Thus, the mu-receptor seems to be the primary opiate receptor involved in the regulation of LH secretion. None of the opiate agonists employed had an effect on FSH secretion.

Animals↗
PubMedDate not supplied

Impact of epidermal growth factor (EGF) radioreceptor analysis on long-term survival of gastric cancer patients.

BACKGROUND: The EGF receptor/ligand system seems to be involved in the regulation of gastric mucosa proliferation and progression of gastric carcinomas. PATIENTS AND METHODS: EGF receptor levels were quantitatively determined in 47 gastric carcinomas by 125J [EGF] radioreceptor assays in membrane preparations of tumor samples or corresponding adjacent mucosa. Specific receptor binding was determined by the analysis of displacement curves by non-linear least-square regression analysis using an estimated model of 'goodness of fit'. RESULTS: Increased EGF receptor binding was observed in gastric carcinomas (mean +/- SEM: 11.87 +/- 1.9 fmol/mg protein) in comparison to adjacent normal gastric mucosa ( 5.28 +/- 1.0 fmol/mg protein, p = 0.003). Elevated EGF receptor levels were especially found in more invasive T3/4 carcinomas, tumors with positive lymph nodes, advanced UICC III carcinomas, undifferentiated tumors, carcinomas of the diffuse-type according to Lauren's classification and gastric carcinomas localized distal from the cardia. In histopathologically normal appearing gastric mucosa, EGF-receptor levels were significantly decreased relative to corresponding tumor samples from advanced UICC stages (UICC I vs UICC I/II: p = 0.008) or tumors with low levels of differentiation (G2 vs G3: p = 0.028). Overall survival was significantly reduced in patients with advanced gastric carcinomas according to UICC classification (UICC III vs UICC I/II: 18.8 vs 45.5 months, p = 0.016). A subgroup analysis of gastric carcinomas localized distal from the cardia indicated, that increased EGF-receptor levels were an independent indicator of poor prognosis as determined by univariate (p = 0.020) and multivariate analysis (p = 0.042). CONCLUSION: Gastric carcinomas with increased EGF receptors might be a possible target for anticancer strategies blocking the EGF receptor/ligand pathway.

Epidermal Growth Factor↗