Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prolonged treatment of cultured rat heart muscle cells containing beta 1- and non-muscle cells containing beta 2-adrenoceptors with beta-adrenoceptor antagonists devoid of intrinsic sympathomimetic activity had no effect on beta-adrenoceptor density. In contrast, antagonists with intrinsic sympathomimetic activity decreased beta-adrenoceptor density and response (adenylate cyclase stimulation) in both heart muscle (beta 1) and non-muscle cells (beta 2) by a maximum of about 50%. An even larger down-regulation of beta-adrenoceptors and loss of receptor-stimulated adenylate cyclase activity was induced by the full endogenous agonist, noradrenaline, with the beta-adrenoceptors of heart muscle cells (beta 1) being much more sensitive to the beta 1-selective noradrenaline than the heart non-muscle cell beta 2-adrenoceptors. When combined with noradrenaline, the antagonists with intrinsic sympathomimetic activity prevented the action of noradrenaline at both beta 1- and beta 2-adrenoceptors, thereby leading to an apparent up-regulation of receptor density and response. This apparent reversal from an agonist to an antagonist action was observed at much lower concentrations of noradrenaline at beta 1- than at beta 2-adrenoceptors. The data presented indicate that the beta-adrenoceptor antagonists with intrinsic sympathomimetic activity, but not those without, upon prolonged treatment decrease the density and responsiveness of both beta 1- and beta 2-adrenoceptors in cultured rat heart cells. This suggests that the intrinsic sympathomimetic activity of these agents is not a subtype-selective component. Furthermore, the agonist and antagonist activity of these agents apparently depends on the concomitant presence of an endogenous full agonist and an its own affinity and that of the partial agonist for the beta-adrenoceptor subtype.
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PMID:Intrinsic sympathomimetic activity of beta-adrenoceptor antagonists: down-regulation of cardiac beta 1- and beta 2-adrenoceptors. 257 97

A growing number of reports have related cocaine use with the onset of myocardial infarction in young otherwise healthy individuals. Although the cardiac effects of cocaine have traditionally been attributed to sympathomimetic stimulation, several studies have suggested that cocaine may be directly cardiotoxic. The purpose of this study was to evaluate the cardiotoxic effects of cocaine in an in vitro preparation devoid of sympathetic innervation. Primary cultures of rat cardiac muscle and non-muscle cells were prepared from hearts excised from 3-5-day-old Sprague-Dawley rats. Cultures were exposed to various cocaine concentrations (1 x 10(-7)-1 x 10(-3)m) for 1-24 hr. Beating activity, morphological status and lactate dehydrogenase (LDH) leakage were evaluated following cocaine exposure. A decrease in the beating activity of cultured muscle cells was observed 1 hr after exposure to the highest cocaine concentrations (1 x 10(-5)-1 x 10(-3)m) tested. Similar results were obtained 24 hr after exposure. Morphological alterations in muscle cells were evident only after exposure to the highest concentration (1 x 10(-3)m). Vacuoles appeared 1 hr after cocaine exposure and were replaced by dark granules within 24 hr. LDH release was significantly elevated in the muscle cell cultures exposed to 1 x 10(-3)m cocaine for 24 hr. The pattern of cocaine-induced morphological alterations and enzyme leakage was similar in non-muscle cells. These data suggest that cocaine induces direct toxic effects on both cardiac muscle and non-muscle cells maintained in an environment free of neuronal and hormonal influences.
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PMID:Cocaine-induced cardiotoxicity in vitro. 2070 36