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Biomedical subjects

G Engel

Publications and source records attributed to G Engel.

At least 73 records · Page 4Linked to original sources
PubMed1985

5-Hydroxytryptamine receptor antagonism by metoclopramide and ICS 205-930 in the guinea-pig leads to enhancement of contractions of stomach muscle strips induced by electrical field stimulation and facilitation of gastric emptying in-vivo.

Contractions induced by electrical field stimulation of isolated circular muscle strips, taken from the guinea-pig stomach, were enhanced by metoclopramide, ICS 205-930 and MDL 72222 at concentrations similar to those shown to antagonize at neuronal 5-hydroxytryptamine receptor sites in a variety of preparations. Metoclopramide, MDL 72222 and ICS 205-930 also facilitated gastric emptying in-vivo. The abilities of metoclopramide, MDL 72222 and ICS 205-930 to enhance stomach muscle contraction processes and to facilitate gastric emptying may be the consequence of 5-hydroxytryptamine receptor antagonism.

Animals↗
PubMed1985

Acute tubular necrosis after inhalation exposure to methylene chloride. Report of a case.

Nephrotoxic reaction occurred after inhalation exposure to methylene chloride. This exposure is associated with acute renal failure, myoglobinuria, hypocomplementemia, and liver enzyme elevations. Pathologic specimens, both light and electron microscopic, demonstrate renal tubular damage. We conclude that methylene chloride may have potential as both a hepatotoxic and nephrotoxic agent when inhaled at high concentrations over an extended period of time.

Acute Kidney Injury↗
PubMed1984

2-[125Iodo]LSD, a new ligand for the characterisation and localisation of 5-HT2 receptors.

LSD was iodinated with Na125I and chloramine T, to get the radioligand [125I]LSD ( 125IOL ) and with N-I-succinimide to obtain the nonradioactive compound 2-I-LSD (IOL) for comparative pharmacological studies. The introduction of iodine in position 2 of LSD leads to an increase in selectivity for 5HT2 receptors. In rat cortex membranes, 125IOL possesses a KD = 0.9 +/- 0.1 nmol/l, Bmax = 240 +/- 20 fmoles/mg, and a nonspecific binding of 30-40% in presence of 100 nmol/l ketanserin. In competition experiments, 5HT antagonists showed monophasic displacement curves. Their KI-values correlate well with pD'2-values for inhibition of 5HT-induced contraction of canine basilar artery. It can be concluded that the sites labelled by 125IOL have pharmacological properties in common with central 5HT2 receptors, which are identical with vascular postjunctional 5HT receptors. The high specific radioactivity of 125IOL permits detection of even small 5HT2 receptor densities which exist in the guinea pig ileum. These 125IOL binding sites are pharmacologically different to those found in the brain or on the vessels and might be a special subpopulation of 5HT2 sites. For example, ketanserin has a high affinity to the sites labelled by 125IOL in the brain and a 100 times lower affinity to the sites labelled in the ileum. In a routine binding screen with various ligands, the inhibition constants of IOL for alpha 1, alpha 2, beta, histamine and muscarinic receptors are greater than 100 nmol/l with the exception for dopamine receptors, 40 nmol/l. 125IOL was employed for the autoradiographic localisation of its binding sites after in vitro labelling of microtome rat brain sections. 125IOL labelled 5HT2 sites in the cortex and dopamine receptors in the nucleus caudatus. The exposure times required were very short, compared to those of other 5HT2 ligands available.

Animals↗
PubMed1984

Labelling of Ri adenosine receptors in rat fat cell membranes with (-)-[125iodo]N6-hydroxyphenylisopropyladenosine.

A new adenosine analogue, (-)-iodo-N6-phydroxyphenylisopropyladenosine [(-)-IHPIA], has been developed for radioligand binding studies of Ri adenosine receptors. In addition, the effects of (-)IHPIA on adenosine-mediated responses of rat fat cells have been characterized. (-)IHPIA is slightly less potent at Ri adenosine receptors than (-)N6-phenylisopropyladenosine [(-)PIA] as assessed by adenylate cyclase and lipolysis studies. (-)IHPIA inhibited basal adenylate cyclase activity with an IC50 of 60 nmol/l compared to an IC50 of 16.3 nmol/l for (-)PIA. (-)PIA and (-)IHPIA inhibited adenosine deaminase-stimulated lipolysis of intact rat fat cells with an IC50 of 0.55 and 3.6 nmol/l. The potency of (-)N6-phydroxyphenylisopropyladenosine [(-)HPIA] was intermediate. (-)HPIA has been labelled with carrier-free Na[125I] to very high specific activity (2,175 Ci/mmol) and used as agonist radioligand in binding studies of Ri adenosine receptors. The binding of (-)[125I]HPIA was saturable, reversible and stereospecific. Saturation analysis revealed two affinity states with dissociation constants (KD) of 0.7 and 7.6 nmol/l and maximal number of binding sites (Bmax) of 0.94 and 0.95 pmol/mg protein. The rate constant of association, k1, was 3.7 X 10(8) l X mol-1 X min-1. Binding was slowly reversible with a t1/2 of 88 min. In competition experiments specific binding was most potently inhibited by (-)PIA, N6-cyclohexyladenosine (CHA), (-)HPIA and (-)IHPIA, followed by 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine. 1,3-Diethyl-8-phenylxanthine (DPX) and 8-phenyltheophylline were the most potent adenosine antagonists with Ki-values of 67 and 83 nmol/l, whereas the methylxanthines 3-isobutyl-1-methylxanthine, theophylline and caffeine had Ki-values between 1 and 21 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1984

Identification of 5HT2-receptors on longitudinal muscle of the guinea pig ileum.

In binding experiments with the radioligands [3H]Ketanserin (HKet) and [125I]LSD (ILSD) 21 compounds were investigated using rat brain cortex membranes. The pKD-values of the compounds were virtually independent of the radioligand used and their rank order was consistent with classification of the binding sites as being of the 5-HT2-type. In contrast, in the longitudinal muscle of the guinea pig ileum in the presence of 0.3 microM cinanserin, ILSD labelled sites which were quite different to those in the cortex. In a functional test antagonism of the 5HT induced contraction of the guinea-pig ileum was measured in the presence of 1 microM atropine. The pharmacological inhibition constants (IC50-values) of 8 compounds correlated well with the dissociation constants for HKet binding in the cortex and did not correlate with the data from ILSD binding in the guinea pig ileum. It is concluded that the ileum contains postjunctional 5HT2-receptors which mediate contraction. The nature of the ILSD binding sites in the ileum remains to be elucidated.

Animals↗
PubMed1984

True uterine diverticulum. A partial müllerian duct duplication?

True uterine diverticulum is an exceedingly rare entity. We report only the second case, to our knowledge, of a nulliparous uterus containing a diverticulum communicating with the endometrial cavity. True uterine diverticula probably arise from a localized duplication of the distal Müllerian duct on one side. They may be confused pathologically with uterine sacculations of pregnancy, but tend to have thicker walls. Associated conditions include "ectopic" pregnancy in the diverticulum, dysmenorrhea, and abnormal uterine bleeding.

Adult↗
PubMed1984

Three distinct subtypes of serotonergic receptors mediate the triphasic blood pressure response to serotonin in rats.

In pentobarbitone- or urethane-anaesthetized normotensive rats the triphasic pressure response to serotonin (5-HT): a short-lasting depressor phase with an intense bradycardia, a pressor phase and a prolonged hypotension, was investigated. The highly selective 5-HTM antagonist ICS 205-930 (1 microgram/kg) inhibited the first but not the second or third phase. The 5-HT2 antagonist ketanserin (0.1 mg/kg) inhibited the second but not the first or third phase. Following selective blockade of the pressor component with ketanserin (0.1 mg/kg), the hypotensive potency of eight serotonin receptor agonists was quantified (-log ED50). A correlation (r = 0.75, P less than 0.05) was observed between this parameter and the displacement of the 5-HT1 ligand [3H]-5-HT. It is suggested that the three phases are due to 5-HTM-, 5-HT2- and 5-HT1-receptor activation, respectively.

Animals↗
PubMed1983

Characterization of beta-adrenergic receptor subtypes in androgen-induced mouse kidney hypertrophy using a new high-affinity ligand, [125I]iodocyanopindolol.

In fully developed androgen-induced hypertrophy of female mouse kidney, beta-adrenergic receptors per unit membrane protein were increased approx. 2.5-fold, as measured by the binding of [125I]iodocyanopindolol, with no change in apparent dissociation constants (Kd range 20-25 pM). Membrane protein relative to total kidney protein, Na+/K+-dependent ATPase (EC 3.6.1.3) and 5'-nucleotidase (EC 3.1.3.5) activities and cholesterol content per unit membrane protein did not differ significantly in preparations from control and treated animals. The binding of iodocyanopindolol to kidney membranes was characterized with respect to association and dissociation kinetics, and also in regard to the less-specific contributions of other major catecholamine or indolamine receptors, using mixtures of the corresponding specific competitors. beta 1-selective drugs, practolol and metoprolol, and beta 2-selective agents, IPS-339 and zinterol, were competed with iodocyanopindolol to assess the receptor type specificity, and the ensuing binding profiles were dissected by a nonlinear regression analysis as described by Munson, P.J. and Rodbard, D. (Anal. Biochem. (1982) 107, 220-239). Most of the androgen-induced beta-adrenergic receptors had the binding properties corresponding to beta 2-subtype. No consistent increase in the density of beta 1-adrenergic receptors could be shown.

Androgens↗
PubMed1983

Evidence for common pharmacological properties of [3H]5-hydroxytryptamine binding sites, presynaptic 5-hydroxytryptamine autoreceptors in CNS and inhibitory presynaptic 5-hydroxytryptamine receptors on sympathetic nerves.

The affinities of 16 5-hydroxytryptamine (5-HT) receptor agonists (indole derivatives) and 7 5-HT receptor antagonists for [3H]5-hydroxytryptamine [( 3H]5-HT) binding sites in rat cerebral cortex membranes were determined. In addition, the potencies of the agonists for inhibiting the electrically induced tritium overflow from rat brain cortex slices preincubated with [3H]5-HT and from canine saphenous veins preincubated with [3H]noradrenaline were measured. Furthermore, the potencies of the indole derivatives for inducing contractile responses of canine saphenous veins were recorded. In addition, the interaction of the antagonists with unlabelled 5-HT at the 5-HT autoreceptor was studied in rat brain cortex slices. There was a good correlation between the binding affinities of the indole derivatives for the [3H]5-HT sites of rat brain cortex membranes and their potencies for inhibiting the evoked tritium overflow from both rat brain cortex slices and strips of canine saphenous vein. Comparison of the inhibition constants derived from the overflow experiments in both tissues again revealed a high correlation coefficient while there was only weak correlation between the binding affinities in rat brain cortex and the contractile potencies of the drugs in canine saphenous vein strips. When 5-HT receptor antagonists were investigated, metitepin and metergoline showed moderate affinities for the 5-HT autoreceptors in rat brain cortex slices, whereas quipazine had only weak affinity, and ketanserin, metoclopramide, cinanserin and cyproheptadine exhibited no antagonistic property. In binding experiments, the competition curves of most 5-HT receptor antagonists were biphasic, suggesting that the [3H]5-HT binding sites are heterogeneous.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Affinity spectra: a novel way for the evaluation of equilibrium binding experiments.

For equilibrium binding isotherms of radioreceptor assays, the affinity spectrum is defined as a plot of the number of binding sites against their corresponding dissociation constants. A numerical procedure for direct calculation of affinity spectra from untransformed binding data is presented and illustrated with experimental values. The advantage of the new method in comparison to non-linear regression analysis is the fact that no starting values and mathematical models have to be supplied and that statistical assessment of the results is straightforward from a detailed graphical display of a likelihood function. Affinity spectra thus show directly all information formerly obtained by means of both graphical plots and regression analysis.

Animals↗
PubMed1983

Evidence for mediation by 5-HT2 receptors of 5-hydroxytryptamine-induced contraction of canine basilar artery.

The agonist potencies of 8 indole derivatives and the potencies of 19 recognized antagonists to inhibit constrictor responses to 5-hydroxytryptamine (5-HT) of canine basilar artery were established. In addition the affinities of the indole derivatives for [3H]5-hydroxytryptamine [( 3H]5-HT) binding sites and the affinities of the antagonists for [125Iodo]LSD [( 125I]LSD) binding sites in rat brain cortex membranes were determined. Comparison was also made between the potencies of the antagonists on canine basilar artery and the KD values published for displacement of [3H]ketanserin binding (Leysen et al. 1982). There was a good correlation between the affinities of the antagonists for 5-HT2 binding sites labelled by both [125I]LSD and [3H]ketanserin and the affinity parameters calculated for inhibition of constrictor responses to 5-HT of canine basilar artery. No correlation could be found between the affinities of the indole derivatives for 5-HT1 binding sites labelled by [3H]5-HT and their potencies to constrict canine basilar artery. It is concluded that constrictor responses to 5-HT of canine basilar artery are mediated by 5-HT2-like receptors.

Animals↗
PubMed1983

Binding of 125I-cyanopindolol to beta-1-adrenoceptors in a high and low affinity state.

Investigation of binding properties of (+), (-) and (+/-) 125Iodocyanopindolol (ICYP) to beta 1-adrenoceptors of guinea pig left ventricle membranes revealed that these radioligands bind to receptors in a high and low affinity state which is not influenced by guanylnucleotides. The contribution of the (+)enantiomer to the binding of the racemic ligand at low receptor concentrations can be neglected since the dissociation time courses of (+/-) and (-) ICYP are identical. The existence of two affinity states of beta-adrenoceptors interacting with the antagonist ICYP was evident from 1: biphasic dissociation kinetics and 2: from curvilinear Scatchard plots.

Animals↗
PubMed1983

Simultaneous differentiation of three opiate receptor subpopulations by computer modelling.

[3H]-(-)-bremazocine was displaced from guinea-pig brain membrane homogenates by three compounds having different specificity to opiate receptor subpopulations. A three site receptor model showed the best fit of the calculated to the measured value for the opiate mu (DAla2,MePhe4,Gly(ol)5-enkephalin) and the delta specific compound (DAla2,DLeu5-enkephalin). Computer modelling of data from displacement curves with the opiate kappa specific compound U-50.488H favored a two site receptor model.

Animals↗
PubMed1983

Selective distribution of beta- and alpha 1-adrenoceptors in rat lung visualized by autoradiography.

The distribution of beta- and alpha 1-adrenoceptors was studied in rat lung by autoradiography using two ligands: 125-Iodocyanopindolol for beta-adrenoceptors, and 125-Iodo-BE 2254 for alpha 1-adrenoceptors. Beta-adrenoceptors were widely distributed in the lung parenchyma and on the walls of the airways (bronchioles). The epithelium of the bronchioles showed a higher density of beta-adrenoceptors than the smooth muscle. The blood vessels (veins) seemed to have very few beta-adrenoceptors. Alpha 1-adrenoceptors were found in approximately ten fold smaller amounts than beta-adrenoceptors in the lung parenchyma and on the small veins. On the bronchioles, an extremely small number of alpha 1-adrenoceptors was visible.

Animals↗
PubMed1983

Growth in the area of the inferior dental foramen of rats.

The object of the present investigation was to see if the bone around the inferior dental nerve remodelled during mandibular growth and development. The investigation was carried out by injecting 27 albino Lewis rats with three fluorescent bone seeking dyes--oxytetracycline HCl (OTC), alizarin red S (ARS), and 2,4 bis-[N,N'-di' (carbomethyl-aminomethyl)] fluorescein (DCAF)--and then studying the bone around the inferior dental foramen. The mandibles of the animals were studied both macroscopically and microscopically under ultraviolet light to investigate the growth processes occurring and to see if the inferior dental foramen was relocated during growth. A quantitative analysis utilizing two specimens was also carried out for the same purpose. The results of both the qualitative and the quantitative analyses showed that the bone around the inferior dental nerve remodeled during mandibular growth. The mandible grew in an upward and backward direction, and the inferior dental foramen was correspondingly relocated in an upward and backward direction to maintain exactly the same position relative to the condyle and the posterior border of the ramus. This study, then, supports Moss's concept of the "unloaded" nerve, and is in keeping with his view of mandibular growth based on the functional matrix theory.

Animals↗