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Biomedical subjects

G Engel

Publications and source records attributed to G Engel.

At least 37 records · Page 2Linked to original sources
PubMed1985

Characterization of the 5-HT1B recognition site in rat brain: binding studies with (-)[125I]iodocyanopindolol.

(-)[125I]Iodocyanopindolol ([125I]CYP) labels rat brain membrane sites which display high affinity for several serotonergic and beta-adrenergic compounds. The binding of [125I]CYP to these serotonergic recognition sites was evaluated in the presence of 30 microM (-)isoprenaline in order to suppress binding to beta-adrenoceptors. [125I]CYP binds in rat cortex membranes rapidly, reversibly and stereoselectively to a finite number of recognition sites: Bmax = 180 fmol/mg, KD = 230 pM. Similar affinity values of [125I]CYP were obtained in membranes from rat hippocampus and striatum. Kinetic, saturation and competition experiments suggest that under these conditions [125I]CYP binds to a single serotonergic recognition site named 5-HT1B. The pharmacological profile of 5-HT1B sites is characteristic of a 5-HT1 binding site and shows the following rank order of affinity for agonists: RU 24969, (5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]1H-indole) greater than 5-CT, (5-carboxamidotryptamine) greater than 5-HT, (5-hydroxytryptamine, serotonin) greater than 5-OCH3-T, (5-methoxytryptamine) much greater than 2-CH3-5-HT, (2-methylserotonin) greater than 8-OH-DPAT, (8-hydroxy-2-(di-n-pro-pylamino)-tetralin). The rank order of affinity for antagonists is: (+/-)ICYP, ((+/- )-3-I-cyano-pindolol) greater than (-)21-009, (4-[3-ter-butyl-amino-2-hydroxy-propoxy]-indol-2-carbonic acid isopropyl ester) greater than (+)21-009 greater than (-)propranolol greater than metitepin greater than (-)pindolol much greater than ketanserin greater than spiroperidol greater than mesulergine. 5-HT1B recognition sites display low affinity for selective beta 1- and beta 2-adrenoceptor antagonists, e.g. atenolol, betaxolol, ICI 89-406 and ICI 118-551. The low affinity of 5-HT1B recognition sites for some 5-HT1A, 5-HT1C and 5-HT2 selective compounds (e.g. 8-OH-DPAT, mesulergine, ketanserin) suggests that 5-HT1B recognition sites are pharmacologically different from 5-HT1A, 5-HT1C and 5-HT2 recognition sites.

Animals↗
PubMed1985

Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig brain membranes: radioligand binding studies with [3H]5-HT, [3H]8-OH-DPAT, (-)[125I]iodocyanopindolol, [3H]mesulergine and [3H]ketanserin.

The pharmacological characteristics of the binding of [3H]8-OH-DPAT ([3H]8-hydroxy-2(di-n-propylamino)tetralin, [125I]CYP ((-)[125I]iodocyanopindolol) (in the presence of 30 microM (-)isoprenaline) and [3H]mesulergine to 5-HT1 recognition sites were studied in rat and pig brain membranes. [3H]8-OH-DPAT bound in rat and pig cortex to the 5-HT1A recognition site characterized by high affinity for 5-CT (5-carboxamido-tryptamine), 8-OH-DPAT, 5-HT (5-hydroxytryptamine, serotonin) and low affinity for pirenperone, ketanserin and mesulergine. [125I]CYP bound in rat but not in pig cortex to the 5-HT1B site which shows high affinity for (-)21-009 (4[3-ter-butyl-amino-2-hydroxy-propoxy]indol-2-carbonic acid isopropyl ester), (+/-)ICYP (3-I-cyanopindolol), 5-HT, RU 24969 (5-methoxy-3-[1,2,3,6-tetrahydropyridon-4-yl]1H-indole) and low affinity for 8-OH-DPAT, mesulergine and pirenperone. [3H]Mesulergine bound in pig choroid plexus and in rat cortex (besides binding to 5-HT2 sites in rat cortex) to the 5-HT1C recognition site characterized by high affinity for metergoline, mesulergine, 5-HT and methergine and low affinity for (-)21-009, ICYP, 8-OH-DPAT and spiroperidol. The pharmacological profile of 5-HT1A sites in rat and pig cortex appears to be identical; 5-HT1C sites in pig choroid plexus and rat cortex show no differences. In contrast, it was not possible to label 5-HT1B sites with [125I]CYP in pig brain membranes indicating that like 5-HT2 receptors, 5-HT1 recognition sites show species differences. The pharmacological profiles of the three 5-HT1 recognition sites are clearly different from one another. Furthermore, the pharmacological profile of each individual 5-HT1 recognition site is also different from that of the 5-HT2 receptors labelled with [3H]ketanserin in rat cortex membranes although some similarities exist between 5-HT2 and 5-HT1C sites. Finally, the beta-adrenoceptor antagonist (-)21-009 which has different affinities for 5-HT1A, 5-HT1B and 5-HT1C recognition sites, yielded triphasic competition curves for [3H]5-HT binding in rat cortex membranes providing evidence that [3H]5-HT labels three distinct 5-HT1 sites in these membranes.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1985

beta-Adrenoceptor blocking agents recognize a subpopulation of serotonin receptors in brain.

The interaction of beta-adrenoceptor blocking agents with serotonin receptors in rat brain was analyzed by quantitative light microscopic autoradiography using (-) [125I]cyanopindolol (ICYP) as a ligand. In some brain areas such as the globus pallidus and dorsal subiculum, binding of ICYP was blocked with high affinity by some serotoninergic ligands, RU-24969 and serotonin, but not by lysergic acid diethylamide and 8-hydroxy-2-(N,N-di-n-propylamino)tetralin. Some beta-blockers also showed high affinity for these sites. These results supply direct evidence for the labeling of a subclass of serotonin receptors, the 5-HT-1B class, providing anatomical and pharmacological basis for some known serotonin-related effects of beta-adrenoceptor drugs.

Adrenergic beta-Antagonists↗
PubMed1985

Lesioning of serotoninergic and noradrenergic nerve fibres of the rat brain does not decrease binding of 3H-clonidine and 3H-rauwolscine to cortical membranes.

alpha 2-Adrenoceptors located presynaptically on nerve terminals are known to modulate the release of neurotransmitters from noradrenergic and serotoninergic neurons. The pre- and/or postsynaptic localization of binding sites for alpha 2-adrenergic radioligands, the agonist 3H-clonidine and the antagonist 3H-rauwolscine, was investigated in the rat cerebral cortex by the use of specific neurotoxins. Intracerebroventricular injections of 6-hydroxydopamine (6-OH-DA) and 5,7-dihydroxytryptamine (5,7-DHT) were used to destroy the noradrenergic and serotoninergic neurons, respectively, and the success of the treatment was controlled by measurement of tritium accumulation in cortex slices incubated with 3H-noradrenaline or 3H-serotonin. In cortical membranes, 3H-rauwolscine bound to a single site (KD about 5 nmol/l; Bmax 217-247 fmoles/mg protein), whereas 3H-clonidine bound to a high affinity site (KD 0.6-1.4 nmol/l) and a low affinity site (KD 6-10 nmol/l). The total number of high plus low affinity 3H-clonidine binding sites was about two thirds of the number of 3H-rauwolscine binding sites. 6-OH-DA treatment significantly increased the number of high affinity 3H-clonidine binding sites without reducing the number of high plus low affinity binding sites, indicating a denervation supersensitivity. KD- as well as Bmax-values for 3H-rauwolscine remained unaltered after 6-OH-DA-treatment. Since an increase in postsynaptic alpha 2-adrenoceptors due to 6-OH-DA-administration might have masked a loss of presynaptic alpha 2-adrenergic binding sites, rats were chronically treated with high doses of clonidine in order to prevent a possible supersensitivity of postsynaptic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1985

beta-Adrenoceptor subtypes in sections of rat and guinea-pig kidney.

The present autoradiographical study examines the distribution of the two beta-adrenoceptor subtypes in sections of rat and guinea-pig kidney. The radioligand [125Iodo]-(--)-cyanopindolol was used for the labelling of beta-adrenoceptors and the selective beta-adrenoceptor blocking agents ICI 89-406 (beta 1-antagonist) and ICI 118-551 (beta 2-antagonist) were utilized to differentiate both subclasses unequivocally. beta-Adrenoceptors in rat kidney were found to be almost exclusively beta 1. They were located mainly on glomeruli and to a lesser extent on the straight part of the distal tubules and on the cortical portion of the collecting ducts. Some beta 2-adrenoceptors were localized around the corticomedullary junction. Grain localization in the auto-radiograms was absent in the inner medulla and papilla. Glomeruli and distal tubules of the guinea-pig kidney also possess only beta 1-adrenoceptors, but, in contrast to the rat, extremely high concentrations of beta 2-adrenoceptors were associated with the straight part of the proximal tubules in the cortex and possibly with the cortical portion of the collecting duct. Labelling was not detected on the proximal convoluted tubule in either species.

Adenylyl Cyclases↗
PubMed1985

Study of the contractile effect of 5-hydroxytryptamine (5-HT) in the isolated longitudinal muscle strip from guinea-pig ileum. Evidence for two distinct release mechanisms.

The contractile effect of 5-HT in the isolated longitudinal ileal muscle of adult guinea-pigs was studied over a large concentration range. 5-HT produced a biphasic concentration-response curve indicative of an interaction with at least two independent populations of receptors. The concentrations which elicited half-maximal effects for the first and the second phases of the concentration-response curve were estimated as 1.5 +/- 1.2 X 10(-8) mol/l and 1.3 +/- 0.4 X 10(-6) mol/l respectively. The maximal response produced by the interaction of 5-HT with the high affinity receptor (i.e. first phase) was calculated as 27 +/- 9.3% of the total response. The biphasic concentration-response was not influenced by methysergide (10(-6) mol/l). The effect of low concentrations of 5-HT (less than 3 X 10(-7) mol/l) was antagonised by atropine (10(-7) mol/l), tetrodotoxin (TTX) (10(-6) mol/l), morphine (10(-5) mol/l), the substance P antagonist, D-Pro4,D-Trp7,9-SP4-11 (3 X 10(-5) mol/l) and capsaicin (10(-5) mol/l). Physostigmine (10(-7) mol/l) augmented the effect. The response to high concentrations of 5-HT (3 X 10(-7)-3 X 10(-6) mol/l) was antagonised by ICS 205-930 and D-Pro4,D-Trp7,9-SP4-11 in a competitive manner and was inhibited by TTX, morphine and capsaicin in an insurmountable way. The effect of very high concentrations of 5-HT (greater than 10(-5) mol/l) could be partially antagonised by methysergide (10(-7) mol/l) in the presence of ICS 205-930 (10(-7) mol/l) and totally by a combination of methysergide and TTX.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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

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↗
PubMed1979

Acid phosphatase.

Acid phosphatase is a ubiquitous lysosomal enzyme that hydrolyses organic phosphates at an acid pH. Although the postpuberteral prostatic epithelial cell contains a uniquely high concentration of acid phosphatase, cellular components of bone, spleen, kidney, liver, intestine, and blood also contain this enzyme. The discovery that prostatic carcinoma cells often retain a high concentration of acid phosphatase characteristic of the normal postpubertal gland led to the recognition of the first clinically useful tumor marker. Recognition that the serum of patients with prostatic malignancy frequently contains an increased concentration of this enzyme has resulted in persistent efforts to identify the source, to accurately quantitate the level of serum acid phosphatase, and to determine the clinical significance of those levels. A variety of enzymatic and immunologic techniques have been employed to measure acid phosphatase. In the past, various substrates and inhibitors were utilized to increase specificity and sensitivity. Emphasis has now shifted to the development of radioimmunoassay and counterimmunoelectrophoresis in an attempt to enhance those parameters. Judgment of their efficacy awaits further testing and evaluation. The clinical significance of normal and abnormal serum acid phosphatase is constantly being reevaluated. In order to maximize the value of laboratory measurements, the clinical and pathologic status of the patient, the techniques employed in obtaining and storing the blood sample and the procedures used in analysis must be known and considered. Traditionally, the serum prostatic acid phosphatase has been thought to originate in the prostatic cancer cell and has been used to stage the disease. Until recently, elevated serum values have been accepted as an indication of extraprostatic disease, and were thought to rule out lesions confined to the prostate. The elevation of acid phosphatase levels in patients with disseminated disease or the failure of elevated levels to return to normal with treatment have been assumed to indicate a poor prognosis. However, unequivocal documentation of the validity of these statements is not available. Newer immunologic techniques for measuring acid phosphatase may significantly alter our current concept of its role as a tumor marker.

Acid Phosphatase↗
PubMed1978

Penile blood pressure in the evaluation of erectile impotence.

Identification of specific etiologies of erectile impotence is hindered by a paucity of objective criteria needed to segregate organic from psychogenic varieties and to define specific organic causes. Simplified measurement of penile blood pressure was performed with a digital cuff and a portable ultrasound Doppler system for flow detection. An index relating penile-to-brachial systolic blood pressure was generated, and the results were compared in patients with impotence versus patients with normal erections. The mean indices for the two groups were significantly different (P less than 0.05). The penile-to-brachial index provides an additional diagnostic tool in the evaluation of potency, allowing us to identify those patients with decreased penile blood flow, and may be helpful in selecting patients for revascularization procedures.

Blood Pressure↗
PubMed1978

Ureterolymphatic backflow.

A case is reported of apparent radiologic demonstration of a communication between a completely obstructed distal ureter and its draining lymphatics in a patient with invasive bladder tumor involving the ureteral orifice.

Aged↗
PubMed1977

[Investigations on the production of mycotoxins and their quantitative analysis. VI. Citreoviridin (author's transl)].

UV-densitometric and fluorodensitometric evaluations of the mycotoxin citreoviridin on thin-layer plates are described. The UV maximum is at 360 nm on thin-layer plates and at 388 nm in ethanolic solution. Its emission maximum has been found to be at 525 nm both in chloroform and on thin-layer plates. The two procedures are similar in their sensitivity. Since the UV-densitometric evaluation is more reliable, it is preferred to fluorodensitometric procedure.

Chromatography, Thin Layer↗