Search PubMed⌕ Search

Biomedical subjects

A W Schmidt

Publications and source records attributed to A W Schmidt.

At least 37 records · Page 2Linked to original sources
PubMed1989

5-Hydroxytryptamine receptor "families".

The identification of multiple receptor subtypes for 5-hydroxytryptamine (5-HT) made by using radioligand binding techniques proliferated at a brisk rate in the 1980s. The application of molecular biological techniques to 5-HT receptor studies is likely to lead to an expansion rather than a reduction in the number of distinct 5-HT receptor subtypes. Although the current status of 5-HT receptor pharmacology may appear to be overwhelmingly confusing to most investigators, the evolving data suggest that 5-HT receptor subtypes can be categorized into three major families. Each family consists of multiple receptor subtypes that share similarities in their molecular biological, pharmacological, biochemical, and/or physiological properties. This review provides a summary of recent data as well as a framework for the classification of 5-HT receptor subtypes.

Animals↗
PubMed1989

The clinical utility of pharmacological agents that act at serotonin receptors.

The past decade has seen important advances in the clinical utility of serotonergic agents. The putative novel anxiolytic effects of 5-HT1A partial agonists such as buspirone, the antidepressant effects of selective serotonin (5-HT) uptake blockers such as fluoxetine, and the unique and potent antiemetic effects of 5-HT3 antagonists in cancer chemotherapy are excellent examples of the clinical relevance of selective 5-HT receptor agents. The increasing ability to modulate serotonergic neurotransmission through distinct 5-HT receptor subtypes should greatly facilitate the analysis of 5-HT in both normal and abnormal human brain function.

Animals↗
PubMed1989

Three-dimensional steric molecular modeling of the 5-hydroxytryptamine3 receptor pharmacophore.

A computer-based three-dimensional steric molecular model of the 5-hydroxytryptamine3 (5-HT3) receptor pharmacophore was defined on the basis of radioligand binding data. Analysis of published data led to the identification of 19 different chemical structures that share only a single known pharmacological property, i.e., less than 10 nM affinity for the 5-HT3 receptor. These 19 compounds were then categorized into seven chemical families, which derive from six main steric "core" structures. From the composite analysis of all 19 potent agents, nine steric chemical criteria were derived, which can be used to describe the 5-HT3 receptor pharmacophore. This information was then used to explain the 5-HT3 receptor inactivity of atrophine, a compound that differs structurally from ICS 205-930 in the steric properties of only a single key atom. The steric chemical information was also used to predict the activity of serotonergic compounds that had never been analyzed at 5-HT3 receptor binding sites. Two serotonergic drugs that meet all nine steric criteria were found to be active at the 5-HT3 receptor binding site (i.e., pizotifen, KI = 42 +/- 10 nM, and clozapine, KI = 52 +/- 8 nM). By contrast, two serotonergic agents that do not meet the criteria were found to be inactive at the 5-HT3 receptor binding site (i.e., ipsapirone and pirenperone, KI values greater than 1000 nM). This computer-based steric molecular modeling approach allows for the analysis and identification of 5-HT3 receptor-active agents with minimal dependence upon animals and radioactive compounds.

Animals↗
PubMed1987

Afferent and efferent connections of the vestibulolateral cerebellum of the little skate, Raja erinacea.

Horseradish peroxidase and cobaltous lysine tracers are used to determine the afferent and efferent projections of the vestibulolateral cerebellum (VLL) in the little skate, Raja erinacea. The skate VLL has separate divisions, pars medialis and pars lateralis, associated with vestibular and lateralis modalities, respectively. The pars medialis has a typical cerebellar structure with molecular and Purkinje cell layers and granular areas. In addition to known inputs from eighth nerve vestibular fibers and limited mechanosensory lateralis afferents, pars medialis afferents are from the ventral part of the descending octaval nucleus, the lateral funicular nucleus and nucleus of the medial longitudinal fasciculus. The pars lateralis and rostral anterior octaval nucleus may be additional afferent sources. Pars medialis efferents project to ventral descending and anterior octaval nuclei, as mossy fibers to the cerebellar corpus and as parallel fibers in the ventrolateral extreme of the molecular layer in the medial octavolateralis nucleus. The pars lateralis comprises granule and Golgi cells and is subdivided into a dorsal granular ridge (DGR) and lateral granular area (LG) that are the sources of parallel fibers in the molecular layers of the dorsal (electrosensory) and medial (mechanosensory) octavolateralis nuclei. Local injections of tracer reveal a systematic topography of pars lateralis parallel fiber projections and a mossy fiber projection to the corpus. Both DGR and LG receive direct spinal input but afferent sources to DGR and LG are otherwise distinct. While LG is known to receive mechanosensory lateralis afferents and limited eighth nerve fibers, DGR receives no direct cranial nerve input. Additional afferents to LG are predominantly from contralateral LG and the anterior octaval and lateral funicular nuclei. Additional DGR afferents are from three medullary nuclei beneath the cerebellar peduncle, nuclei F and K and paralemniscal nucleus, which also projects directly to the dorsal nucleus. Distinct inputs to DGR and LG suggest different contributions of VLL to medullary processing in electro- and mechanoreception.

Animals↗
PubMed1984

Somatotopy within the medullary electrosensory nucleus of the little skate, Raja erinacea.

The dorsal octavolateral nucleus is the primary electrosensory nucleus in the elasmobranch medulla. We have studied the topographic organization of electrosensory afferent projections within the dorsal nucleus of the little skate, Raja erinacea, by anatomical (HRP) and physiological experiments. The electrosensory organs (ampullae of Lorenzini) in skates are located in four groups on each side of the body, and each group is innervated by a separate ramus of the anterior lateral line nerve (ALLN). Transganglionic transport of HRP in individual rami demonstrated that electroreceptor afferents in each ramus project to a separate, nonoverlapping division of the central zone of the ipsilateral dorsal nucleus. These divisions, which are distinct areas separated by compact cell plates, are somatopically arranged. The volume of each division of the dorsal nucleus that is related to a single ramus is proportional to the number of ampullae innervated by the ramus, but not to the body surface area on which the receptors are distributed. Nearly one-half of the nucleus is devoted to electrosensory inputs from the buccal and superficial ophthalmic ampullae concentrated in a small area on the ventral surface of the head rostral to the mouth. Multiple and single unit recordings demonstrated that adjacent cells in the nucleus have similar receptive fields on the body surface and revealed a detailed point-to-point somatotopy within the nucleus. With threshold stimuli most single units have ipsilateral receptive fields made up by excitatory inputs from 2-5 ampullary organs. The somatotopy within the mechanosensory medial nucleus, also revealed by the HRP fills of individual ALLN rami, appears less rigid than that in the dorsal nucleus, as extensive overlap is present in the terminal fields of separate ALLN rami.

Afferent Pathways↗
PubMed1976

[The experimental examination of the effect on the uterine blood flow of angiotensin II during pregnancy (author's transl)].

In experiments with animals it was investigated the endurance of the myometrial and the blood flow of the renal cortex during endogenous pressure substances. At the same time it was tested, if treatment with sexual hormones or a pregnancy had the tested principles and changes through pressure substances, and that the changes were significant. The investigations were conducted on three groups of female rabbits. The blood changes in myometrial and in the uterine were measured and continually registered with the special heated thermistor, from the principle of the thermoclearance. The success of the blood pressure was intraarterial measured with an electric mechanism. Precisely the same doses (in relativity of the animals weight) of pressure substances were applied with an infusions pump intravenously. And pressure substances Angiotensin II, Norepinephrine and Epinephrine, and their actions on the blood pressure and blood flow through the myometrium and through the renal cortex were examined. Altogether 131 values were registered. The results of the study that were statistically secure were as follows: a) The uterine blood flow pro tissue volume unit stays constant also by pregnancy or pseudopregnancy. b) The blood flow of the kidney is perhaps twice as high as the myometrial. c) The myometrial blood flow is with the arterial systolic blood pressure tightly correlated. Blood pressure increases through Angiotensin-infusion and also recovery of the uterine blood flow. d) An autoregulation of the uterine blood flow is not observed. e) The decrease of the renal blood flow after the giving of pressure substances was not modified through pregnancy. f) In quality the behaviour of the organ blood flow is the same after applied infusion of the pressure substances. Quantity differences exist however between Angiotensin II, Norepinephrine and Epinephrine. The method of measuring the blood flow through the uterus and in the kidney was placed in one view there. The finding of another examination groups for the problem of the organ blood flow in pregnancy was under critical consideration the methods combined and in connection with the proper examinations discussed. Till now in the theory over the cause of EPH-syndrom the predominate recently compiled comprehensive summary was; the proper body pressure substances--especially from the renin Angiotensin system--after chronical invoices it was decides diminished uterus blood flow appeared. After the earlier results were not all secure. The proper examination speech was therefore, that regarding the kidney function relevant alterations, also unter the conditions of pregnancy, are to be observed. The pressure dependant regulation of myometrial blood flow without proving autoregulation required however another test of the predominante gestose theory.

Angiotensin II↗