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D Hoyer

Publications and source records attributed to D Hoyer.

At least 145 records · Page 8Linked to original sources
PubMed1991

5-HT1-like receptors mediate 5-hydroxytryptamine-induced contraction of guinea-pig isolated iliac artery.

1. The effects of 5-hydroxytryptamine (5-HT) and of the 5-HT1-like receptor agonists, 5-carboxamidotryptamine (5-CT) and sumatriptan (GR43175) were investigated in isolated ring preparations of guinea-pig common iliac artery. 2. The three agonists induced very weak, if any, contractions of unstimulated preparations, whereas they elicited concentration-dependent contractions in preparations given a moderate tone by a threshold concentration of prostaglandin F2 alpha (PGF2 alpha). 3. Under the latter conditions, Emax values for 5-HT and 5-CT reached about 45% of PGF2 alpha maximal effect, whereas the Emax value of sumatriptan was significantly lower (about 35%). The rank order of potency (mean EC50 value, nM) was 5-CT (6.6) greater than 5-HT (22.9) greater than sumatriptan (155). Pargyline, cocaine or deoxycorticosterone were without significant effect on the contractions induced by 5-HT. 4. The 5-HT3 receptor antagonist, (1 alpha H, 3 alpha,5 alpha H-tropan-3-yl) 1-H-indole-3-carboxylic acid ester (ICS 205-930; 1 microM), had no effect on 5-HT-, 5-CT- and sumatriptan-induced contractions. 5. The 5-HT2 receptor antagonist, ketanserin (1 microM) caused only small rightward shifts (concentration-ratios, about 2) in the concentration-response curves to 5-HT, 5-CT and sumatriptan without significantly depressing the maximum effects. 6. In the presence of ketanserin (1 microM), the non-selective 5-HT receptor antagonist, methiothepin (0.1 microM), shifted the concentration-response curves to 5-HT and 5-CT to the right in a parallel manner and to a similar extent for both agonists (respective mean pKB values, 8.07 and 8.27). The effect of sumatriptan was also antagonized by methiothepin, but solvent effects precluded quantitative analysis of this antagonism. 7. It is concluded that 5-HT1-like receptors mediate the contractions induced by 5-HT, 5-CT and sumatriptan in guinea-pig isolated iliac artery. For reasons not yet understood, these receptors are detected only when the tissues are moderately pre-contracted by PGF2alpha.

Animals↗
PubMed1991

5-HT receptors: subtypes and second messengers.

Our knowledge about 5-HT (serotonin, 5-hydroxytryptamine) receptors has gained significantly over the recent few years. The discovery of selective ligands and the use of new techniques have led to a significant increase in the number of recognised receptors subtypes. The present status of awareness is largely related to the use of radioligand binding studies, autoradiography, second messenger analysis and more recently, molecular biological techniques. Three main families of 5-HT receptors, of which subtypes have been described, are now accepted. This heterogeneity is further substantiated by the cloning of the cDNA's of three different 5-HT receptors. This article reviews some of the recent developments which led to the characterisation of 5-HT receptor subtypes.

Adenylyl Cyclases↗
PubMed1991

Experimental and clinical studies of neonatal eeg mapping--methodical prerequisites and data interpretation.

To investigate whether the sampling theorem was fulfilled up to now in experimental and clinical EEG-mapping of neonates and to determine the "smearing effect" of EEG transmission by the leading media up to the skin, EEG-maps from 5 slightly anaesthetized term newborn piglets and 8 healthy human newborns were calculated. A spatial sampling rate of 1-2 cycles per cm is necessary for a sufficient reproduction of surface EEG topology in newborn piglets showing activity maxima within motor projection zones. In human neonates, 8-channel mapping gave insufficient results, whereas state and EEG pattern related 16-channel maps provided sufficiently constant, but not complete pattern. Simultaneous maps from epidural and epiossal, and epiossal, and surface recordings in newborn piglets showed only small "smearing" effects. We conclude, the more topical interpretation chances exist, like in neonates with smaller "smearing" effects of transmission media, the more complete uptake of original data for mapping is necessary. Up to now, it is done seldomly.

Animals↗
PubMed1990

Similar distribution of [125I]sarafotoxin-6b and [125I]endothelin-1, -2, -3 binding sites in the human kidney.

The distribution of binding sites for 125I-labelled endothelins (ET-1, ET-2, ET-3) and sarafotoxin-6b (SRTX-6b) was visualized in human kidneys using autoradiography. The glomeruli, the internal medulla and the renal blood vessels presented the highest levels of labelling, while the outer medulla exhibited intermediate and the cortex lower densities of sites. The relative enrichment of binding sites in different renal areas was similar for each peptide, suggesting the existence of a homogeneous population of endothelin/sarafotoxin receptors.

Aged↗
PubMed1990

Subtypes of alpha 1-adrenoceptors in hippocampus of pigs, guinea-pigs, calves and humans: regional differences.

Radioligand binding studies were performed with membranes of guinea-pig, pig, calf and human hippocampus using [125I]BE 2254 (also known as [125I]HEAT) as the radioligand. [125I]BE 2254 bound with similar high affinity to saturable populations of recognition sites in all four membrane preparations. Competition curves obtained with a variety of ligands (e.g., WB 4101, benoxathian, 5-methyl-urapidil) were biphasic and the profiles of the high- and low-affinity components of [125I]BE 2254 binding were similar in all four membrane preparations. The data suggest that [125I]BE 2254 labels two subtypes of alpha 1-adrenoceptors in the hippocampus of these species. [3H]WB 4101 was used to label alpha 1A recognition sites in pig hippocampus membranes. [3H]WB 4101 recognized with high affinity an apparently homogeneous class of sites, as suggested by monophasic saturation and competition experiments. The rank order of affinity of the compounds for the high-affinity component of [125I]BE 2254 binding was similar to the rank order of affinity of these drugs for [3H]WB 4101 sites. The pharmacological profile of the low-affinity component of [125I]BE 2254 binding was similar to that described recently for the alpha 1B-adrenoceptor cloned from DDT1 cells. In autoradiographic studies with human hippocampal slices, CEC (chloroethylclonidine), an alkylating agent described to show selectivity for alpha 1B-adrenoceptors, displaced preferentially [125I]BE 2254 binding from the molecular layer of the dentate gyrus. In contrast, WB 4101 an alpha 1A-adrenoceptor-selective ligand, displaced preferentially [125I]BE 2254 binding in the hilus and the CA3 region. The data show that 2 subtypes of alpha 1-adrenergic recognition sites can be identified in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1990

The serotonin 5-HT1D receptor: a progress review.

Most of the known neurotransmitters interact with more than one type of receptor. Some of them even dispose of receptor subtypes to exert their actions. Serotonin, far from being an exception to that, possesses at least 3 classes of receptors, which have all been reported to be heterogeneous, although convincing data only exist for the 5-HT1 class. This name has been proposed in 1979, two years before the introduction of 'A' and 'B' in the nomenclature to account for the observed heterogeneity of these sites. The 5-HT1C receptor subtype was first described in 1984 and the last member of the family, named 5-HT1D, was characterized in 1987. The pharmacological profiles, the signal transducing systems and the anatomical localizations, both at the regional and cellular levels, of all these subtypes have been investigated and possible functions have been proposed for each of them. Moreover, last and most definitive demonstration of the subtype individuality, the gene or complementary DNA coding for the 5-HT1A and 5-HT1C (and 5-HT2) receptors have been cloned and sequenced. Such data are still missing for 5-HT1D (and 5-HT1B) receptors, but will certainly be provided in the next few years. However and waiting for this decisive clue, the characterization of the 5-HT1D subtype leaves no doubt concerning its significance as a function 5-HT receptor. This review will concentrate on the characteristics of this subtype of 5-HT receptor.

Animals↗
PubMed1990

Determination of regional blood flow in abdominal organs and other structures in normal female rats and in rats with TAA-induced chronic liver injury using 99mTc labelled HSA-microsphere technique.

A method for simultaneous determination of cardiac output and regional blood flow distribution in a chronically instrumented, unrestrained rat preparation for different experimental conditions (i.e. conscious, free movement; general anesthesia) and in an experimental chronic liver injury model is described. The use of a modified radioactive microsphere reference sample method using 99mTc labelled HSA-microspheres provides valid measurements of cardiac output [255 +/- 21.6 ml/(min.kg b.wt.)] and of the determined blood flow rates of abdominal organs (with separate determination of arterial and portal-venous hepatic blood flow rates; the latter by means of arterial blood flow measurement of the gastrointestinal tract and the spleen), the myocard, the adrenals, the kidneys, and various brain regions. Furthermore, it is demonstrated that this measuring approach with chronical preparation can also advantageously be used in pharmacological or pathogenetical studies, especially because of the simple measuring equipment and the comparatively low costs that offer a broader application.

Abdomen↗
PubMed1990

Receptor modification in the brains of spontaneously hypertensive and Wistar-Kyoto rats: regionally specific and selective increase in cerebellar beta 2-adrenoceptors.

Quantitative in vitro autoradiography was used to study beta-adrenergic and benzodiazepine receptor density in discrete regions from sagittal brain sections of 20 week old hypertensive (SHR) and normotensive (WKY) rats. The density of beta-adrenoceptors was increased by 68% in the granule cell layer of the cerebellum of the SHR without a change in receptor affinity; this increase was specific for receptors of the beta 2-subtype. On the other hand, benzodiazepine receptor density was unchanged in the cerebella of SHR. These results indicate that brain beta-adrenoceptors are differentially modulated by the hypertensive state which may be either a cause or a consequence of alterations in adrenergic nervous system activity found in the SHR.

Animals↗
PubMed1990

Serotonin 5-HT1D receptors.

5-HT receptors are subdivided into 3 families, 5-HT1, 5-HT2, and 5-HT3, of which subtypes have been described. The 5-HT receptor field has experienced over the last 10 years a revival due to the availability of new and more selective drugs and new techniques. This communication deals essentially with the biochemical approaches to characterize 5-HT1D receptors, and their comparison with 5-HT1B receptors. The methods used include radioligand binding, in vitro autoradiography, and second messenger studies. 5-HT1 receptor subtypes are labeled with [3H]5-HT and present a large heterogeneity: no less than 4 subtypes have been characterized: 5-HT1B and 5-HT1D are labeled respectively with [125I]cyanopindolol, and [3H]5-HT under appropriate conditions. Although some similarities are evident, the pharmacology of the two receptors is clearly different. Rat 5-HT1B receptors recognize with high affinity a number of beta-adrenoceptor antagonists, such as SDZ 21-009, cyanopindolol, pindolol, propranolol and isamoltane. In contrast, calf, pig or human 5-HT1D receptors show significantly lower affinities for these drugs. 5-HT1D receptors show high to intermediate affinities to compounds such as PAPP, DP-5-CT, 8-OH-DPAT, yohimbine and rauwolscine, whereas 5-HT1B receptors have very low affinities for these compounds. The presence of 5-HT1B receptors has been documented convincingly only in rat, mouse and hamster. 5-HT1D receptors have been demonstrated in pigeon, guinea-pig, cat, dog, pig, calf, monkey, and man. The distribution of 5-HT1B and 5-HT1D receptors in all species examined so far, is very similar: high concentrations of sites are found in the nigro-striatal pathway, caudate-putamen, globus pallidus and especially substantia nigra. The subicullum shows also high densities of sites. Similar functional correlates have been proposed to 5-HT1B and 5-HT1D sites. Thus, 5-HT1D receptors are negatively coupled to adenylate cyclase in guinea-pig and calf substantia nigra, and 5-HT1B receptors are negatively coupled to adenylate cyclase in rat substantia nigra. Further, it is established that terminal 5-HT autoreceptors are of the 5-HT1B type in rat cortex, and of the 5-HT1D type in guinea-pig, pig, human and possibly rabbit cortex. In the rat saphenous vein, 5-HT1B receptors mediate inhibition of noradrenaline release. Preliminary evidence suggests that the canine basilar artery and saphenous vein, described as models for "5-HT1-like" receptors, could contain 5-HT1D receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMed1990

[Adaptative procedures for pre-processing of evoked potentials].

The investigation of evoked potentials requires suitable consideration of physiological and pathophysiological characteristics of spontaneous and evoked electrical activity of the brain. For this purpose a preprocessing strategy based on adaptive recursive estimation of statistical parameters was developed. In this way, artifact handling, classification, filtering and further preprocessing of spontaneous EEG and evoked potentials can be improved.

Algorithms↗
PubMed1990

5-Hydroxytryptamine (5-HT)-induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT1D receptor subtype.

The 5-hydroxytryptamine (5-HT) receptor mediating endothelium-dependent relaxation of pig coronary arteries was characterized using a variety of 5-HT receptor agonists and antagonists. Unrubbed (with endothelium preserved) rings precontracted by prostaglandin F2 alpha in the presence of ketanserin relaxed in an endothelium-dependent manner to 5-HT, 5-carboxamidotryptamine and 5-methoxytryptamine with about equal potency and efficacy. By comparison, bufotenine, 3-(dimethylamino)ethyl-N-methyl-1H-indole-5-methane sulfonamide, (-)-alpha-methyl-5-HT,N,N-dipropyl-5-carboxamidotryptamine and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole were half-efficient and other drugs [in particular the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin] were inactive as agonists up to 0.1 mM. The effect of 5-carboxamidotryptamine was antagonized in an apparently competitive manner by 15 drugs. Among the most potent antagonists (mean pKB value) were the nonselective 5-HT receptor antagonists, methiothepin (7.30) and metergoline (6.86), the 5-HT1A/5-HT1D receptor ligand, 1-[2-(4-amino-phenyl)ethyl]-4-(3-trifluoromethylphenyl)-piperazine (7.02), the 5-HT1A/5-HT1B/5-HT1D receptor ligand, 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2,-a]quinoxaline 1 (6.73) and yohimbine (6.37). Selective ligands for 5-HT1A receptors were either inactive [8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide] or poorly active (spiperone, 4.44). Beta-adrenoceptor antagonists with affinity for 5-HT1A and 5-HT1B receptors weakly antagonized the effect of 5-carboxamidotryptamine (pKB values less than or equal to 5.32), as did the 5-HT1c/5-HT2 receptor antagonist, mesulergine (5.30) and the yohimbine isomer, corynanthine (4.85). Methysergide was clearly a noncompetitive antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

[EEG and evoked potential mapping].

By spectral EEG-mapping and EP-mapping, especially the topologic dimension of electrical brain activity can be evaluated for clinical use. On the other hand, this method allows the highest solution from all functional imaging procedures within the time dimension of brain activity. On the other hand, the ability of topological solution is limited. But the latter is probably better than hitherto assumed and surprisingly well at least regarding neonates. However, several methodological prerequisites described here must be fulfilled. From the pathophysiological point of view, the limits must be considered besides the diagnostic possibilities. Meanwhile, spectral EEG-mapping and EP-mapping are diagnostically used in all main fields of traditional EEG-analysis, like seizures and in the preadiagnostics of tumors a.o. Also in the diagnostics of cerebrovascular disease including transient ischemic attacks, the EEG-mapping and/or EP-mapping are useful within the total diagnostics. There is a similar situation in the diagnostics of degenerative brain disorders. But the significance of frequently described changes inpsychoses, partly also neuroses and other functional disorders is not clear. Altogether, this non-invasive, economically most favourable method for the functional imaging procedures in brain diagnostics is promising to extent the routine diagnostics also to a more precise manner.

Brain↗
PubMed1989

[3H]ICS 205-930 labels 5-HT3 recognition sites in membranes of cat and rabbit vagus nerve and superior cervical ganglion.

The binding characteristics of [3H]ICS 205-930, a 5-hydroxytryptamine 5-HT3 receptor antagonist, were investigated in membranes prepared from cat and rabbit vagus nerve (VN) and superior cervical ganglion (SCG). The autoradiographic localisation of 5-HT3 recognition sites was also assessed using [3H]ICS 205-930 in slices from cat medulla oblongata, nodose ganglion and vagus nerve. [3H]ICS 205-930 bound to a homogeneous population of high affinity recognition sites in cat VN: Bmax = 201 +/- 43 fmol/mg protein, pKD = 9.26 +/- 0.17 and SCG: Bmax = 291 +/- 40 fmol/mg, pKD = 9.35 +/- 0.80 (n = 3). Competition experiments performed in membranes from cat VN and SCG with agonists and antagonists suggested the presence of a homogeneous population of [3H]ICS 205-930 recognition sites. Competition curves were steep and monophasic and were best fitted by a 1 receptor site model. The following rank order of affinity for [3H]ICS 205-930 binding sites was observed with antagonists: SDZ 206-830 = ICS 205-930 greater than BRL 43694 greater than SDZ 206-792 greater than quipazine greater than MDL 72222 greater than metoclopramide greater than mCPP and agonists: 2-methyl-5-HT = 5-HT greater than phenylbiguanide. A similar profile was observed for a limited series of compounds in rabbit membranes. Drugs acting at 5-HT1, 5-HT2 and dopamine receptors (domperidone, spiperone and metergoline) showed very low affinities for [3H]ICS 205-930 recognition sites. The sites labelled with [3H]ICS 205-930 in vagus nerve and superior cervical ganglion of both species displayed the pharmacological profile of a 5-HT3 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

5-Hydroxytryptamine 5-HT1B and 5-HT1D receptors mediating inhibition of adenylate cyclase activity. Pharmacological comparison with special reference to the effects of yohimbine, rauwolscine and some beta-adrenoceptor antagonists.

5-Hydroxytryptamine1B (5-HT1B) receptor mediated-inhibition of forskolin-stimulated adenylate cyclase activity in rat substantia nigra was characterized pharmacologically and compared to 5-HT1D receptor mediated-inhibition of forskolin-stimulated adenylate cyclase activity in calf substantia nigra. Special attention was paid to the effects of drugs known to bind with high affinity to 5-HT1B (pindolol, propranolol, cyanopindolol, SDZ 21-009, isamoltane) or 5-HT1D recognition sites (yohimbine, rauwolscine). pEC50 or pKB values of a variety of 5-HT-receptor ligands (6 agonists including 5-HT, and 12 antagonists) for the inhibition of adenylate cyclase activity in rat substantia nigra, correlated significantly to the corresponding pKD values at 5-HT1B binding sites (r = 0.90, P = 0.0001). Amongst the alpha 2- and beta-adrenoceptor antagonists tested, none of the drugs expressed more than 35% of the intrinsic activity of 5-HT at 5-HT1B receptors. When tested as antagonists, their pKB values were in good agreement with their pKD values for 5-HT1B sites. By contrast, these drugs displayed marked intrinsic activity at 5-HT1D receptors: their pEC50 values were close to their pKD values for 5-HT1D sites and their effects could be potently antagonized by methiothepin. The rank orders of potency of the tested compounds at 5-HT1B and 5-HT1D were markedly different. The results strengthen the identity between 5-HT receptors mediating inhibition of adenylate cyclase activity in rat and calf substantia nigra and 5-HT1B and 5-HT1D binding sites, respectively. They underline the differences between these receptors in terms of intrinsic activities and potencies of drugs.

Adenylyl Cyclase Inhibitors↗