Clinical and experimental pharmacology & physiology. Supplement最新文献

{"title":"7th International Conference on Peripheral Dopamine. Dublin, Ireland, 3-5 August 1998. Proceedings and abstracts.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"26 ","pages":"S1-76"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21349015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological importance of dopamine as a noradrenaline precursor in the corpus luteum.","authors":"J Kotwica,&nbsp;M Bogacki","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1. Both in vivo and in vitro studies have demonstrated that the adrenergic innervation of the ovary affects corpus luteum (CL) secretory function in many species. 2. In cattle, ovarian noradrenergic stimulation or the administration of noradrenaline (NA) to the ovary increases ovarian oxytocin (OT) secretion and post-translational processing of OT synthesis within a few minutes. Furthermore, NA affects both progesterone release and its synthesis by increasing cytochrome P450sec and 3 beta-hydroxysteroid dehydrogenase activity. This effect is mediated via luteal cell beta 1- and beta 2-adrenoceptors. 3. The total number of luteal beta-adrenoceptors correlates with peripheral progesterone concentrations during the luteal phase. Conversely, ovarian denervation causes a decrease of steroidogenic activity in the corpus luteum, an increase in beta-adrenoceptors on luteal cells, a delay in follicular development and the disruption of cyclicity, as well as other effects. Moreover, brief pharmacological blockade of ovarian beta-adrenoceptors in the mid-cycle of cattle decreases progesterone secretion by 20-40%. 4. We conclude that tonic beta-adrenoceptor stimulation of the CL ensures the basal secretion of progesterone, whereas acute noradrenergic activation supports the CL during stressful situations that could impair its function. Dopamine concentrations within the CL are highly correlated with those of NA during the oestrous cycle and are higher in the newly formed compared with the developed CL, the regressed CL or the CL of pregnant females.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"26 ","pages":"S29-35"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21253667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-atherosclerotic action of vascular D1 receptors.","authors":"K Yasunari,&nbsp;M Kohno,&nbsp;H Kano,&nbsp;T Hanehira,&nbsp;M Minami,&nbsp;J Yoshikawa","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1. Vascular smooth muscle cell (VSMC) migration and proliferation are believed to play key roles in atherosclerosis. To elucidate the role of vascular dopamine D1-like (D1 and D5) receptors in atherosclerosis, the effects of dopamine and the specific D1-like receptor agonists SKF 38393 and YM 435 on platelet-derived growth factor (PDGF)-BB-mediated VSMC migration, proliferation and hypertrophy were investigated. 2. We observed that cell stimulated by 5 ng/mL PDGF-BB showed increased migration, proliferation and hypertrophy. These effects were prevented by co-incubation with dopamine, SKF 38393 or YM 435 at 1-10 mumol/L and this prevention was reversed by Sch 23390 (1-10 mumol/L), a specific D1-like receptor antagonist. These actions of D1-like receptor agonists were mimicked by 1-10 mumol/L forskolin, a direct activator of adenylate cyclase, and 0.1-1 mmol/L 8-bromo-cAMP. The actions were blocked by the specific protein kinase A (PKA) inhibitor N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline-sulphonamide (H 89), but were not blocked by its negative control N-[2-(N-formyl-p-chlorocinnamylamino) ethyl]-5-isoquinoline sulphonamide (H 85). Platelet-derived growth factor-BB (5 ng/mL)-mediated activation of phospholipase D (PLD), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activity was significantly suppressed by co-incubation with dopamine. 3. These results suggest that vascular D1-like receptor agonists inhibit migration, proliferation and hypertrophy of VSMC, possibly through the activation of PKA and the suppression of activated PLD, PKC and MAPK activity.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"26 ","pages":"S36-40"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21253668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agonism and inverse agonism at dopamine D2-like receptors.","authors":"P G Strange","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1. The processes that follow the binding of ligands to receptors are critical for their physiological functions. In the present paper I intend to review our own work and the work of other laboratories attempting to understand these processes for the dopamine D2-like receptors (D2, D3, D4) and how they contribute to the mechanisms of drug action. It is thought that the key event in agonist action for these receptors is the stabilization, by the agonist, of the agonist-receptor-G-protein ternary complex. The majority of the work I shall describe has been performed using recombinant receptors expressed in cell lines and the mechanisms of receptor action have been probed using ligand binding (competition vs [3H]-spiperone), the stimulation of [35S]-GTP gamma S binding and inhibition of adenylyl cyclase. 2. Measures of the ability of agonists to stabilize the agonist-receptor-G-protein ternary complex may be obtained in ligand-binding studies using the ratio of dissociation constants for the higher and lower affinity states (KI/KH ratio). The stimulation of [35S]-GTP gamma S binding provides a very convenient assay for agonist action and allows the determination of agonist potency and maximal response. Estimates of these quantities may also be obtained from the inhibition of adenylyl cyclase. For a range of agonists at the D2 receptor, there is a tendency for high values of KI/KH to predict high maximal activity and vice versa, but there is no general correlation. This suggests that the simple scheme of agonist action depending on the stabilization of the ternary complex is an over-simplification and further efficacy determining steps need to be included. For a number of receptors, including the D2 and D3 receptors, it has now been shown that there is activity in the absence of agonist (so-called constitutive activity). This agonist-independent activity can be inhibited by compounds previously considered to be antagonists (e.g. the antipsychotic drugs). Therefore, these compounds are inverse agonists rather than antagonists. The mechanism of this inverse agonist effect is unclear and we are examining this using a variety of biochemical approaches, including the use of constitutively active mutants. 3. The mechanisms of agonism and inverse agonism may be probed using biochemical assays and these studies are of great relevance to the understanding of drug action.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"26 ","pages":"S3-9"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21254360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of dopamine in the pathogenesis of hypertension.","authors":"P A Jose,&nbsp;G M Eisner,&nbsp;R A Felder","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1. Dopamine, via different dopamine receptor subtypes, regulates cardiovascular functions by actions on the central and peripheral nervous systems, vascular smooth muscle, the heart and the kidney. The dopaminergic system in the central nervous system (CNS) may participate in the regulation of systemic blood pressure. 2. Dopamine 'D2-like' (D2, D3 and D4) receptors, rather than 'D1-like' (D1 and D5) receptors, are involved in the CNS regulation of blood pressure; post-synaptic D2-like receptors increase blood pressure, while presynaptic D2-like receptors (the predominant action) produce the opposite effect. 3. Outside the CNS, dopamine may regulate blood pressure via pressure controls that act with intermediate rapidity (e.g. stress relaxation, arginine vasopressin and renin-angiotensin vasoconstriction), as well as those systems related to the long-term control of body fluid volume. 4. Dopamine D1- and D2-like receptors have been described in resistance vessels, such as the renal, mesenteric, coronary, pulmonary and cerebral arteries. The ability of D1-like receptors to inhibit renal smooth muscle hypertrophy indicates their importance in longer-term regulation of blood pressure. 5. Aberrant dopaminergic regulation of aldosterone secretion, via D2-like receptors, has been reported to be involved in some forms of hyperaldosteronism and hypertension. Some forms of hypertension may also be caused by an aberrant renal dopaminergic system. Abnormalities of three aspects of the renal dopaminergic system may lead to hypertension: (i) renal production of dopamine; (ii) transduction of the renal vascular dopamine signal; and (iii) transduction of the renal tubular dopamine signal. 6. Thus, increased blood pressure occurs after either blockade of D1-like receptors or of dopamine production in rats or disruption of the D1 receptor or the D3 receptor gene in mice.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"26 ","pages":"S10-3"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21254363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine sulphate: an enigma resolved.","authors":"G Eisenhofer,&nbsp;M W Coughtrie,&nbsp;D S Goldstein","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1. The source and physiological significance of dopamine (DA) sulphate, which exists in plasma at much higher concentrations than free DA, have long been a puzzle. The present article reviews how the convergence of modern molecular and traditional clinical approaches is shedding new light on the origins and meaning of DA sulphate. 2. The sulphotransferase isoenzyme responsible for production of DA sulphate in humans (SULT1A3) has been cloned and shown to be expressed in large quantities in the gastro-intestinal tract, but not in liver. No orthologue of SULT1A3 has yet been identified in other species, consistent with the greater importance of sulphate conjugation of DA in humans than in most animals. 3. Diet has a major impact on plasma DA sulphate, with dramatic increases after ingestion of meals and foods rich in biogenic amines; however, substantial amounts of DA sulphate remaining after prolonged fasting indicate the presence of a mainly endogenous source. The lack of influence of acute or chronic changes in sympathetic outflow or of sympathoneural degeneration on plasma DA sulphate indicates that DA sulphate does not derive from sympathetic nerve. Relatively low rates of production from intravenously infused DA indicate that very little DA sulphate (< 2%) derives from metabolism of circulating DA, such as in red cells or platelets. 4. Consistent increments in DA sulphate from arterial to the outflowing venous plasma draining mesenteric organs, without increments across other organs or tissues (e.g., heart, lungs, liver), indicate that the gastrointestinal tract is a major source of more than 75% of DA sulphate produced in the body. The gastro-intestinal tract is also the site of a novel DA autocrine/paracrine system that produces nearly 50% of the DA in the body. Therefore, production of DA sulphate appears to reflect an enzymatic 'gut-blood' barrier for detoxifying dietary biogenic amines and delimiting autocrine/paracrine effects of endogenous DA generated in a novel 'third catecholamine system'.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"26 ","pages":"S41-53"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21253669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proceedings of the John Coghlan Festschrift Symposium. Future Perspectives in Molecular Endocrinology. Melbourne, Australia, 30-31 October 1997.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"25 ","pages":"S1-118"},"PeriodicalIF":0.0,"publicationDate":"1998-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20831320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presence of angiotensin II AT2 receptor binding sites in the adventitia of human kidney vasculature.","authors":"J Zhuo,&nbsp;R Dean,&nbsp;D MacGregor,&nbsp;D Alcorn,&nbsp;F A Mendelsohn","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1. Angiotensin II (AngII) receptor subtypes in adult human kidney were pharmacologically characterized by in vitro autoradiography using the AngII receptor subtype-selective antagonists, losartan and PD 123319, and the sensitivity to the reducing agent, dithiothreitol. 2. High densities of AngII AT1 receptor binding occur in the glomeruli and the inner stripe of the outer medulla, while a moderate AT1 receptor binding is localized in the proximal convoluted tubules. 3. AT2 receptor binding is observed predominantly in the intrarenal large blood vessels, including the arcuate, inter- and intra-lobular arteries, and in the renal capsule. 4. In the major renal artery, AT1 receptor binding is abundant in the media and adventitia, while AT2 receptor binding is observed mainly in the adventitia. 5. At the light microscopic level using emulsion autoradiography, AT1 receptors are localized in the glomeruli and juxtaglomerular apparatus, as expected. However, in larger renal blood vessels, including the arcuate arteries, inter- and intra-lobular arteries, intense AT2 receptor labelling occurs primarily in the adventitia, while the endothelium and vascular smooth muscle layers contain only low levels of AngII receptor binding. 6. These results indicate that the adult human kidney displays two pharmacologically distinct AngII receptor subtypes, with AT1 predominating in the glomeruli, juxtaglomerular apparatus, proximal tubules and the inner stripe of the outer medulla, while AT2 predominates in the adventitia of the arcuate and interlobular arteries and the renal capsule. The functional significance of AT2 receptor binding sites in the adventitia of adult human kidney vessels remains to be elucidated.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"3 ","pages":"S147-54"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19956578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics. Proceedings of a symposium. Melbourne, Australia, December 1995.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"3 ","pages":"S57-154"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20027881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functions of angiotensin peptides in the rostral ventrolateral medulla.","authors":"R A Dampney, Y Hirooka, P D Potts, G A Head","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1. It was first shown several years ago that the rostral part of the ventrolateral medulla (VLM) contains a high density of receptor binding sites for angiotensin II (AngII). In the present paper we briefly review recent studies aimed at determining the actions of both exogenous and endogenous angiotensin peptides in the rostral VLM, as well as their specific sites of action. 2. The results of these studies have shown that angiotensin peptides can excite pressor and sympathoexcitatory neurons in the rostral VLM, but do not appear to affect non-cardiovascular neurons in this region. 3. It is known that pressor neurons in the rostral VLM include both catecholamine and non-catecholamine neurons. There is evidence that, at least in conscious rabbits, both of these types of neurons are activated by AngII. The specific endogenous angiotensin peptide or peptides that affect pressor neurons in the rostral VLM have not yet been definitively identified. 4. It is also possible that different angiotensin peptides may have different effects on pressor neurons in the rostral VLM, mediated by different receptors. Further studies will be needed to define these different functions as well as the specific receptors and cellular mechanisms that subserve them.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"3 ","pages":"S105-11"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19953897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}