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Biomedical subjects

G Lambrecht

Publications and source records attributed to G Lambrecht.

At least 109 records · Page 6Linked to original sources
PubMed1987

Binding of the S(+)- and R(-)-enantiomers of bethanechol to muscarinic receptors in jejunal smooth muscle, nasal mucosa, atrial and ventricular myocardium of the rat.

Both the enantiomers of bethanechol displaced R(-)-[3H]quinuclidinyl benzilate from muscarinic binding sites in homogenates from rat jejunum, nasal mucosa, atrial and ventricular myocardium. Stereoselectivity of receptor binding for S(+)- and R(-)-bethanechol was found in all tissues investigated (Ki S(+) less than Ki R(-)). Different proportions of high and low affinity binding sites for bethanechol enantiomers and S(+)-methacholine in jejunal smooth muscle, atrial and ventricular muscle and the presence of only low affinity binding sites in nasal mucosa point to differences in receptor-effector coupling in these tissues. The relative insensitivity of cardiac tissue for bethanechol compared to methacholine might be related to the much smaller proportion of high affinity binding sites found for S(+)-bethanechol in heart ventricular muscle.

Animals↗
PubMed1987

Stimulation of ganglionic muscarinic M1 receptors by a series of tertiary arecaidine and isoarecaidine esters in the pithed rat.

The cardiovascular effects of a series of tertiary esters of arecaidine (1-methyl-1,2,5,6-tetrahydro-3-carboxy-pyridine) and isoarecaidine (1-methyl-1,2,5,6-tetrahydro-4-carboxy-pyridine) were investigated in the pithed rat. For some esters (e.g. arecoline, arecaidine propargyl ester, isoarecoline) a prominent elevation in mean arterial pressure and heart rate was observed following an initial short-lasting and atropine-sensitive depressor response and bradycardia (dose range: 0.1-10 mumol/kg i.v.). The increase in blood pressure and heart rate was not affected by pretreatment with mecamylamine (0.5 and 5 mg/kg i.v.), but could be totally blocked by N-methylatropine (500 micrograms/kg i.v.). Furthermore, the M1 receptor antagonist pirenzepine (300 micrograms/kg i.v.) selectively antagonized these stimulatory cardiovascular responses, indicating that these effects are due to an activation of muscarinic M1 receptors in sympathetic ganglia. As tertiary arecaidine and isoarecaidine esters easily penetrate the blood-brain barrier, they might also stimulate central M1 receptors and thus become lead compounds in the search for an effective drug treatment of Alzheimer's disease.

Animals↗
PubMed1986

Muscarinic ganglionic stimulants: conformationally restrained analogues related to [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride.

The synthesis of a series of tertiary and quaternary cyclic analogues (isoarecolinol, dihydroisoarecolinol, arecolinol, and 3-pyrroline-3-carbinol derivatives) of [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride (McN-A-343) (1), a selective stimulant of muscarinic receptors in sympathetic ganglia (so-called M1 receptors), is reported. The compounds 3-10 were tested for muscarinic ganglion-stimulating activity by recording blood pressure responses in pithed rats. All tertiary compounds tested had no ganglion-stimulating activity. Among the series of quaternary derivatives, only the isoarecolinol analogues 4a and 4b showed considerable ganglion-stimulating effects, whereas the dihydroisoarecolinol (8), the arecolinol (6a, 6b), and the 3-pyrroline-3-carbinol derivatives (10) were much less potent. Our experiments therefore demonstrate that in this series a quaternary nitrogen atom, unsaturation at C2 of the ammonium side chain, and a certain spatial arrangement of the ammonium and the phenylcarbamate groups are essential for potent M1-receptor stimulating activity.

Animals↗
PubMed1986

Kadsurenone distinguishes between different platelet activating factor receptor subtypes on macrophages and polymorphonuclear leucocytes.

The effects of the antagonist kadsurenone on the platelet activating factor (Paf)-induced chemiluminescence of guinea-pig peritoneal macrophages and on pig peripheral blood leucocyte aggregation were compared. Linearity and slopes of unity of the Schild plots confirmed the competitive nature of the antagonism by kadsurenone. pA2 values indicated a 91 fold lower affinity of kadsurenone for leucocyte Paf receptors than for those in macrophages. It is concluded that these two types of Paf receptors are not identical and are provisionally designated Paf1 and Paf2 receptors, respectively.

Animals↗
PubMed1985

The effects of racemic bethanechol and its (R)- and (S)-enantiomers on pre- and postjunctional muscarine receptors in the guinea-pig ileum.

The effect of racemic bethanechol and its (R)- and (S)-enantiomers on smooth muscle contraction and outflow of [3H]-acetylcholine were studied in the guinea-pig myenteric plexus-longitudinal muscle preparation that had been preincubated with [3H]-choline. (S)-, racemic, and (R)-bethanechol caused concentration-dependent contractions of the longitudinal muscle. The potency ratio of the strong isomer (S) to the weak one (R) was 915. Racemic and (S)-bethanechol concentration-dependently inhibited the evoked outflow of [3H]-acetylcholine. Racemic bethanechol was more potent than (S)-bethanechol. (R)-bethanechol up to a concentration of 1 mM did no affect the evoked outflow of [3H]-acetylcholine. (S)-bethanechol was a substrate, and (R)-bethanechol a weak inhibitor of the tissue cholinesterases. The weak cholinesterase-inhibiting action of the (R)-enantiomer probably reinforces the prejunctional effects of the (S)-enantiomer in the racemic mixture.

Animals↗
PubMed1985

Intestinal and serum antibody response in gnotobiotic piglets to oral immunization with Escherichia coli.

The local and systemic immune response to a formolized E. coli oral vaccine was investigated in 13 gnotobiotic piglets. Beginning at ten days of age animals received a daily dose of 10(10) or 10(11) bacteria, on ten consecutive days. Intestinal loop tests with one animal of each group on day 26 showed protection which was more pronounced in the animal dosed 10(10) bacteria compared with the other immunized piglet. Immunoglobulin class-specific antibodies to O and K antigens were determined by ELISA technique. In serum no IgG or IgA antibodies were found, whereas IgM-anti O149 antibodies in both immunized groups reached their highest level at day 4 of dosing and decreased thereafter. IgM-anti K88 antibodies were first detected at day 10 of dosing. Both immunized groups had comparable serum levels at days 20 and 30. Also in gut secretion the IgM antibody response was predominant, and higher levels were found in the 10(10) group than in the 10(11) group. IgG and IgA antibody response were also detected in secretion.

Animals↗
PubMed1984

Comparison of affinities of muscarinic antagonists to pre- and postjunctional receptors in the guinea-pig ileum.

The myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum was preincubated with [3H]choline, then superfused and stimulated electrically (1 Hz 120 pulses). Oxotremorine reduced the evoked outflow of [3H]acetylcholine in a concentration-dependent manner. Each of the six antagonists (scopolamine, methylatropine, trihexyphenidyl, 4-DAMP, clozapine, pirenzipine) produced parallel shifts of the concentration-response curves for the prejunctional effects of oxotremorine. Similarly, in contraction experiments, the antagonists competitively antagonized the postjunctional responses to oxotremorine. The pre- and postjunctional pA2 values did not differ significantly for any of the antagonists. It is concluded that pre- and postjunctional muscarinic receptors in the guinea-pig ileum are pharmacologically similar.

Acetylcholine↗
PubMed1984

A comparison of the antimuscarinic effects of pirenzepine and N-methylatropine on ganglionic and vascular muscarinic receptors in the rat.

The antimuscarinic properties of pirenzepine and N-methylatropine were evaluated in two intact preparations by measuring A) the inhibition of increase in mean arterial pressure evoked by McN-A-343 in pithed rats through activation of ganglionic muscarinic receptors and B) the inhibition of fall in arterial pressure evoked by methacholine in anaesthetized rats through activation of vascular muscarinic receptors. To characterize the antimuscarinic potencies of pirenzepine and N-methylatropine, for both antagonists doses were calculated that produce a 10-fold shift to the right of the dose-response curves for A) the pressor response to McN-A-343 (i.v. administration) in pithed rats (D10-p.r.) and B) for the depressor effect to methacholine (i.v. administration) in anaesthetized rats (D10-an.r.), respectively. Whereas N-methylatropine was virtually equieffective in blocking both muscarinic responses (D10-an.r./D10-p.r. approximately equal to 1), pirenzepine, however, was considerably more potent at ganglionic than at vascular muscarinic receptors (D10-an.r./D10-p.r. approximately equal to 16). These data confirm the existence of excitatory ganglionic muscarinic receptors with high affinity for pirenzepine (M1) and provide evidence for the presence of M2 receptors - receptors which show a low sensitivity to pirenzepine - on vascular smooth muscle cells. To further characterize the anticholinergic properties of pirenzepine, its effect on the pressor response to DMPP, a nicotinic ganglionic stimulant, was investigated in pithed rats. A high dose of pirenzepine (1.13 mumol/kg), given i.v., did not affect nicotinic ganglionic transmission.

Animals↗
PubMed1984

[Critical evaluation of quantitative immunoglobulin determination in the calf].

From 3 calves fed with a single limited amount of colostrum 68 blood serum samples were tested comparatively by single radial immunodiffusion (RID) and by nephelometry for their IgG1-, IgA- and IgM-content. In comparison with nephelometry the commercial available RID kits seemed to be insufficient due to deficient agarose plates, difficulties in diluting, and weak reference sera. The results obtained by RID, therefore, were not comparable with those obtained by nephelometry which should be optimized, too.

Animals↗
PubMed1983

[Not Available].

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History, Modern 1601-↗
PubMed1983

[Structure- and conformation-activity relationships of heterocyclic acetylcholine analogues. 16. Conformational behaviour and cholinergic properties of isoarecaidine and sulfoisoarecaidine esters].

In the course of investigations of structure- and conformation-activity relationships of heterocyclic acetylcholine analogues, both the methyl esters of the tertiary and quaternary isoarecaidine and the sulfoisoarecoline were tested for their cholinergic properties. The electronic structures and the conformational behaviour of these cholinergics were investigated by quantum chemical calculations using Extended Hückel Theory (EHT) and Complete Neglect of Differential Overlap (CNDO/2)MO methods. The results show that the muscarinic potency of the heterocyclic compounds is dependent on structure and conformational behaviour of the onium center. The divergent charge distribution around the cationic heads of the ammonium and sulfonium derivatives, respectively, as well as differences in the dimensions of the two heterocyclic systems, can not be utilized to explain the differences in muscarinic potency of the isoarecaidine and sulfoisoarecaidine methyl esters.

Acetylcholine↗
PubMed1983

[Structure- and conformation-activity relationships of heterocyclic acetylcholine analogs. 17. Conformational behavior and cholinergic properties of arecaidine and sulfoarecaidine esters].

In the course of investigations of structure and conformation-activity relationships of heterocyclic acetylcholine analogues, the tertiary and quaternary methyl esters of arecaidine and the methyl ester of sulfoarecaidine were tested for their cholinergic activities. The conformational behaviour and the electronic structures of these cholinergics were investigated by quantum chemical calculations using Extended Hückel Theory (EHT) and Complete Neglect of Differential Overlap (CNDO/2)methods. The results show that the muscarinic potency of the heterocyclic analogues is dependent on structure and conformational behaviour of the onium center. The divergent charge distribution around the cationic heads of the ammonium and sulfonium derivatives, respectively, as well as differences in the dimensions of the two heterocyclic systems, can not be utilized to explain the differences in muscarinic potency of the arecaidine and sulfoarecaidine methyl esters.

Acetylcholinesterase↗