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Biomedical subjects

G Engel

Publications and source records attributed to G Engel.

At least 19 recordsLinked to original sources
PubMed1992

Elevated stromelysin-1 and reduced collagenase-IV expression in invasive rat embryo fibroblasts expressing E1A deletion mutants + T24-H-ras.

We have studied the in vitro invasive properties of 3 cell lines derived from the co-transfection of rat embryo fibroblasts (REF) with EIA genes deficient in exon 2 and T24-ras. All 3 cell lines showed invasive properties at passage 10 after isolation. Invasive cells expressed elevated levels of stromelysin-1 and reduced levels of 68-kDa type-IV collagenase compared with untransfected REF. In 2 cell lines the invasive capacity increased during in vitro propagation. The expression of stromelysin-1 increased during this process, whereas 68-kDa type-IV collagenase was persistently expressed at reduced levels. In the third clone analyzed, the invasive capacity decreased during culture, in parallel with decreased expression of stromelysin-1. The low level of stromelysin-1 expression observed in this cell line did not result from loss of AP-1-transcription-factor activity, and was not reversed by phorbol-ester treatment.

Adenovirus Early Proteins↗
PubMed1991

Heat resistance of ascospores of Byssochlamys nivea in milk and cream.

Byssochlamys nivea strains of rather varying origin used for heat inactivation experiments were cultured for 28 days at 30 degrees C on malt extract agar, since under these conditions the highest degree of heat resistance of the ascospores was observed. Inactivation was performed in steel capillary tubes to obtain reproducible results under experimental conditions comparable to those prevailing in practice. An inactivation temperature of 92 degrees C proved to be most practical. Decimal reduction times for the individual strains at this temperature in Ringer's solution varied between 1.3 and 2.4 s. In the temperature range studied, inactivation of ascospores in UHT milk (1.5% w/w fat content) and cream (10% w/w fat content) has not been found to differ significantly from that in Ringer's solution. Homogenization of milk as applied in practice did not affect heat inactivation of ascospores. Assuming the most unfavorable conditions (50 ascospores/l and using the most heat-resistant strain) the following relations between the level of infected 500 g packages were calculated: 1 of 10(6) packs infected; 24 s at 92 degrees C; 1 of 10(3) packs infected; 16.5 s at 92 degrees C; 1 of 10(2) packs infected, 14 s at 92 degrees C.

Animals↗
PubMed1991

Conservative management of a combined endodontic-orthodontic lesion.

Pulp injury may occur during orthodontic tooth movement particularly in previously traumatized teeth. Therefore the management of such cases requires specific therapeutic considerations. An extensive periradicular lesion was detected in an orthodontically treated maxillary incisor with an uncertain history of a previous traumatic incident. Conservative endodontic therapy resolved the periradicular lesion thus enabling the orthodontic treatment to continue uneventfully. It is essential to closely monitor the patients undergoing orthodontic treatment and those who are in retention, particularly if a history of trauma is suspected.

Adolescent↗
PubMed1989

5-HT1 receptor agonists attenuate the naloxone-induced jumping behaviour in morphine-dependent mice.

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and RU 24969 have been used to investigate whether 5-HT1A and 5-HT1B receptors are involved in the naloxone-induced jumping behaviour of the chronically morphine-dependent mouse. To control for possible interactions with catecholaminergic systems, the effects of alpha 1- and alpha 2-adrenoceptor antagonists were investigated. 8-OH-DPAT and RU 24969, as well as buspirone, ipsapirone and flesinoxan, were found to suppress jumping. The effects were mimicked by the alpha-adrenoceptor antagonists, idazoxan, WY 26392, yohimbine and rauwolscine. Inhibition of 5-HT synthesis with para-chlorophenylalanine (pCPA) had only minimal effects on withdrawal jumping per se; the attenuating effects of 8-OH-DPAT and RU 24969 were not altered in pCPA-pretreated animals. The effects of RU 24969 were blocked by (-)-pindolol and, stereoselectively, by (-)-SDZ 21-009. (-)-Pindolol neither influenced the action of 8-OH-DPAT nor showed any effect per se. The actions of 8-OH-DPAT and buspirone, but not of RU 24969 and idazoxan, were blocked by the 5-HT1A receptor antagonist, spiroperidol. Similarly, both haloperidol and prazosin prevented the attenuating action of 8-OH-DPAT but did not interfere with the action of RU 24969. We conclude that the actions of 8-OH-DPAT and RU 24969 are mediated by postsynaptic receptors. The 5-HT1B receptor appears to mediate the attenuating action of RU 24969; the exact mechanism of action of 8-OH-DPAT remains open but activation of an alpha 1-adrenoceptor is implicated.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Characterization of an endothelial 5-hydroxytryptamine (5-HT) receptor mediating relaxation of the porcine coronary artery.

The pharmacological properties of the endothelial 5-hydroxytryptamine (5-HT) receptors involved in relaxation of vascular smooth muscle were determined in rings of pig coronary artery contracted with 10 nmol/l of the thromboxane A2 receptor agonist 9,11-dideoxy-11 alpha,9 alpha-epoxy-methano-prostaglandin F2 alpha (U 46619). (1) In the presence of 10 mumol/l ketanserin, relaxation was obtained with: 5-HT (apparent pD2 value 7.00), 5-carboxamidotryptamine (5-CONH2-T; 6.42), 5-aminotryptamine (5-NH2-T; 5.96), 5-methoxytryptamine (5-OCH3-T; 5.92), tryptamine, 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline maleate (CGS 12066 A) and 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969). The maximum relaxation obtainable with the agonists was about 40-60% of the U 46619-induced contraction and the concentration-response curves for 5-HT, 5-NH2-T and 5-OCH3-T were bell-shaped. The endothelium-dependence of this effect (i.e. the failure to relax the artery in endothelium-denuded preparations) was demonstrated for 5-HT, 5-CONH2-T, RU 24969, CGS 12066A and tryptamine. (2) 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 4-hydroxytryptamine, quipazine and yohimbine were ineffective in decreasing the tension of arteries with or without endothelium. Ipsapirone elicited full relaxation of U 46619-induced contraction, but this effect was not endothelium-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Inhibition of the 5-HT-induced cardiogenic hypertensive chemoreflex by the selective 5-HT3 receptor antagonist ICS 205-930.

We investigated the effect of ICS 205-930 [(3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester], a selective antagonist at 5-HT3 receptors, on the cardiogenic hypertensive chemoreflex in the anaesthetized dog. The reflex was elicited by injection of 5-HT (12.5-1600 micrograms) into the left cardiac ventricle and consisted of a dose-dependent systemic hypertension associated with a decrease in heart rate. ICS 205-930 (10, 30, and 100 micrograms/kg i.v.) caused a displacement to the right of both the dose-response curves of 5-HT-induced blood pressure increase and heart rate reduction. Its blocking effects upon the action of 5-HT could be surmounted by increasing the dose of the agonist. The selective 5-HT2 receptor antagonist, ketanserin (0.1 mg/kg i.v.) and the combined 5-HT1 and 5-HT2 receptor antagonist, methiothepin (0.1 mg/kg i.v.) had no influence on the hypertensive reflex. When the reflex was elicited by the ganglionic stimulant, 1,1-dimethyl-4-phenyl-piperazinium (DMPP; 100-1600 micrograms), ICS 205-930 had no blocking effect. The results suggest that the 5-HT-induced cardiogenic hypertensive chemoreflex is mediated by 5-HT3 receptors.

Animals↗
PubMed1988

Characterisation of 5-HT3 recognition sites in membranes of NG 108-15 neuroblastoma-glioma cells with [3H]ICS 205-930.

1. The binding characteristics of [3H]ICS 205-930, a potent and selective 5-hydroxytryptamine 5-HT3 receptor antagonist, were investigated in membranes prepared from murine neuroblastoma-glioma NG 108-15 cells. 2. [3H]ICS 205-930 bound rapidly, reversibly and stereoselectively to a homogeneous population of high affinity recognition sites: Bmax = 58 +/- 3 fmol/mg protein, pKD = 9.01 +/- 0.08 (n = 11). Non linear regression and Scatchard analysis of saturation data suggested the existence of a single class of [3H]ICS 205-930 recognition sites on NG 108-15 cells. The binding was rapid, stable and reversible. The affinity of [3H]ICS 205-930 determined in kinetic studies was in agreement with that obtained under equilibrium conditions. 3. Competition studies performed with a variety of agonists and antagonists also suggested the presence of a homogeneous population of [3H]ICS 205-930 recognition sites. All competition curves were steep and monophasic and were best fit by a 1 receptor site model. [3H]ICS 205-930 binding sites displayed the pharmacological profile of a 5-HT3 receptor. Potent 5-HT3 receptor antagonists showed nanomolar affinities for [3H]ICS 205-930 binding sites with the following rank order of potency: SDZ 206-830 greater than ICS 205-930 greater than SDZ 206-792 greater than BRL 43694 greater than quipazine greater than BRL 24924 greater than SDZ 210-204 greater than MDL 72222 greater than SDZ 210-205. Metoclopramide, mCP and mianserin showed submicromolar affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[3H]ketanserin labels serotonin 5-HT2 and alpha 1-adrenergic receptors in human brain cortex.

The binding of [3H]ketanserin and [125I]BE 2254 [( beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone) was characterized in human brain cortex membranes. As observed in saturation experiments, [3H]ketanserin (a reportedly selective serotonin 5-HT2 ligand) and [125I]BE 2254 (a selective alpha 1-adrenergic antagonists) labeled, apparently, a homogeneous class of high-affinity recognition sites. Competition experiments performed with [125I]BE 2254 and a series of 20 structurally different compounds resulted in steep and monophasic competition curves. In contrast, competition curves of these compounds for [3H]ketanserin binding were often shallow or biphasic, suggesting a heterogeneity of the sites labeled by [3H]ketanserin. In particular, alpha-adrenoceptor-selective ligands (e.g., prazosin, BE 2254, WB 4101, phentolamine) showed clearly biphasic curves displacing about 20% of [3H]ketanserin binding with nanomolar affinity. On the other hand, cinanserin, a selective 5-HT2 antagonist, showed nanomolar affinity for 80% of the sites labeled by [3H]ketanserin, and micromolar affinity for the other 20%. There was a highly significant correlation between [125I]BE 2254 binding and the minor component of [3H]ketanserin in human brain cortex membranes (r = 0.910, p less than 0.0001, n = 20). The data show that [3H]ketanserin binds in the nanomolar concentration range (1.5-1.8 nM) to both 5-HT2 and alpha 1-adrenergic receptors. Similar results were obtained in rat and pig brain membranes. The data suggest that ketanserin possesses a rather limited degree of selectivity in human tissue.

Binding, Competitive↗
PubMed1986

Inhibition of 5-carboxamidotryptamine-induced relaxation of guinea-pig ileum correlates with [125I]LSD binding.

5-Hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), 8-OH-DPAT and RU 24969 relax the guinea-pig ileum precontracted with histamine. This relaxation was characterized using 5-CT as agonist with a series of 8 competitive antagonists. [125I]LSD binding was measured in a membrane preparation of the longitudinal muscle of the guinea-pig ileum in the presence of 3 X 10(-7) M cinanserin in order to suppress binding to 5-HT2 receptors. There was a significant correlation (P less than 0.01) between the antagonism of 5-CT-induced relaxation (pA2 values) and the affinity values of the antagonists for [125I]LSD binding (pKD values). It was also shown that 5-CT relaxed histamine-precontracted longitudinal muscle strips of the guinea-pig ileum. The results suggest that the 5-HT receptor-mediating relaxation in the guinea-pig ileum can be labelled with [125I]LSD and that this receptor does not belong to the 5-HT2, 5-HT1A, 5-HT1B or 5-HT1C receptor subtypes.

Animals↗
PubMed1986

[125I]LSD labels 5-HT1C recognition sites in pig choroid plexus membranes. Comparison with [3H]mesulergine and [3H]5-HT binding.

The mammalian choroid plexus is enriched in a newly described serotonin recognition site, the 5-HT1C site. In order to further characterize these sites, the binding characteristics of [125I]LSD, [3H]mesulergine and [3H]serotonin to pig choroid plexus membranes were compared. These ligands labelled with high affinity a similar number of sites. The binding profiles of the sites labelled with these radioligands are indistinguishable as illustrated by highly significant correlation parameters. These sites are very similar to those labelled by N1-methyl-2-[125I]LSD in pig and rat choroid plexus membranes. The data demonstrate that these ligands label 5-HT1C recognition sites in pig and rat choroid plexus membranes.

Animals↗
PubMed1986

5-HT1A-receptors mediate stimulation of adenylate cyclase in rat hippocampus.

Serotonin (5-HT) stimulated adenylate cyclase activity in homogenates of rat hippocampus. This effect was pharmacologically characterised with a series of agonists and antagonists of various structural classes. These compounds where also tested in radioligand binding studies using selective ligands for the various subtypes of 5-HT1 and 5-HT2 receptors. 5-HT1A, 5-HT1B and 5-HT1C recognition sites were labelled with [3H]8-OH-DPAT([3H]8-hydroxy-2-(di-n-propylamino)-tetralin) in pig cortex membranes, [125I]CYP([125I]iodocyanopindolol) in rat cortex and [3H]mesulergine in pig choroid plexus membranes, respectively. The rank order of potency of 13 agonists stimulating adenylate cyclase activity in homogenates of rat hippocampus was in good agreement with the rank order of affinity of these agonists for the 5-HT1A binding site: N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) greater than 5-carboxamidotryptamine (5-CT) greater than 8-OH-DPAT greater than 5-HT greater than 5-methoxytryptamine (5-OCH3T) greater than d-LSD greater than 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969) greater than alpha-methylserotonin (alpha-CH3-5-HT) greater than dopamine greater than 2-methylserotonin (2-CH3-5-HT). The correlation between the respective potencies and affinities of these agonists was r = 0.934, P less than 0.001. There was no correlation between stimulation of adenylate cyclase activity by these agonists and their affinity for 5-HT1B, 5-HT1C or 5-HT2 binding sites. r = 0.381-0.108, P less than 0.20-0.73.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1986

Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites.

In rat brain cortex slices preincubated with [3H]5-HT, the potencies of 17 5-HT receptor agonists to inhibit the electrically evoked 3H overflow and the affinities of 13 antagonists (including several beta-adrenoceptor blocking agents) to antagonize competitively the inhibitory effect of unlabelled 5-HT on evoked 3H overflow were determined. The affinities of the compounds for 5-HT1B and 5-HT2 binding sites in rat brain cortex membranes (labelled by [125I]cyanopindolol = [125I]-CYP in the presence of 30 mumol/l isoprenaline and [3H]ketanserin, respectively), for 5-HT1A binding sites in pig and rat brain cortex membranes (labelled by [3H]8-hydroxy-2-(di-n-propylamino)tetralin = [3H]8-OH-DPAT) and for 5-HT1C binding sites in pig choroid plexus membranes (labelled by [3H]mesulergine) were also determined. The affinities of the drugs for the various 5-HT recognition sites ranged over 4-5 log units (the functional experiments revealed the same range of differences between the drugs). There were no significant correlations between the affinities of the drugs at 5-HT1C and 5-HT2 binding sites and their potencies or affinities, determined for the 5-HT autoreceptors. In contrast, significant correlations were found between the potencies or affinities of the drugs for the autoreceptors and their affinities at 5-HT1A or 5-HT1B binding sites; the best correlations were obtained with the 5-HT1B binding site. Some of the drugs investigated were not included in the correlation since their agonistic or antagonistic effects on the autoreceptors were weak and pEC30 or apparent pA2 values could not be determined (less than 5.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine.

As a result of controversy in the literature regarding the classification and nomenclature of functional receptors for 5-hydroxytryptamine (5-HT), a framework for classification is proposed. The formulation of these proposals has only been made possible by the recent advent of new drug tools. It is considered that there are three main types of 5-HT receptor, two of which have been well characterised pharmacologically, using selective antagonists, and which it is proposed to name 5-HT2 and 5-HT3. These two groups broadly encompass the "D" and "M" receptors, respectively, which Gaddum identified in the guinea-pig ileum (Gaddum and Picarelli, 1957). The 5-HT2 receptor, which mediates a variety of actions of 5-HT, has been definitively shown to correlate with the 5-HT2 binding site in the brain. No binding studies in brain tissue have yet been published with radiolabelled ligands specific for 5-HT3 receptors. A number of other actions of 5-HT appear to be mediated via receptors distinct from 5-HT2 or 5-HT3 receptors. Since selective antagonists are not yet available, these receptors cannot be definitively characterised, although in many cases they do have some similarities with 5-HT1 binding sites, which are a heterogeneous entity. Criteria are proposed for tentatively classifying these receptors as "5-HT1-like" (Table 1). Definitive characterisation of these receptors will await the identification of specific antagonists. This classification of 5-HT receptors into three main groups (Table 1) is based largely, but not exclusively, on data from studies in isolated peripheral tissues where definitive classification is possible. However, it is believed that this working classification will be relevant to functional responses to 5-HT in the central nervous system.

Animals↗
PubMed1986

Relationship between plasma concentrations and cardiac beta-adrenoceptor blockade--a study with oral and intravenous bopindolol.

Bopindolol, an esterified beta-adrenoceptor blocking drug, was administered to nine healthy male volunteers in oral (1 mg and 4 mg) and intravenous (1 mg) doses. Plasma concentrations determined using a radio-receptor assay (RRA) and high pressure liquid chromatography (h.p.l.c.) yielded almost identical results, indicating that hydrolysed bopindolol, the major metabolite, is responsible for the pharmacological activity of the drug. After intravenous administration the half-life for the formation of the hydrolysis product was about 0.3 h. The elimination of hydrolysed bopindolol from the plasma, determined with a one-compartment model occurred with a half-life of about 4 h. There were indications for a longer beta phase of elimination with a half-life of about 8 h, which, owing to the relative insensitivity of the method for concentrations present after more than 24 h, could not be determined exactly. The absolute bioavailability of the active compound is about 70%. Cardiac beta-adrenoceptor blockade was determined as the reduction in exercise-induced tachycardia. With oral doses the maximum effect was reached after 3 h (-29 beats min-1 after 1 mg, -40 beats min-1 after 4 mg). After intravenous administration most of the effect was present after 0.5 h but the maximum effect (-33 beats min-1) was only reached at 3 h. Bopindolol possesses a long duration of action: after 48 h 33% of the maximum effect of the oral dose of 4 mg was still present.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗