Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocrine responses to the serotonin (5-HT) 5-HT1C/5-HT2 agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were utilised to evaluate cocaine-induced alterations in postsynaptic 5-HT receptor function. Rats received cocaine HCl (0, 5 or 15 mg/kg i.p.) twice daily for 7 days. Effects of DOI (0, 0.5, 2 or 10 mg/kg i.p.) on plasma adrenocorticotropic hormone (ACTH), corticosterone, prolactin, oxytocin and renin concentrations were assessed 42 h after the final cocaine injection. DOI dose dependently increased the plasma concentrations of each hormone. Cocaine potentiated the DOI-induced elevations of plasma ACTH, corticosterone and prolactin concentrations. In contrast, the oxytocin response was reduced, and the renin response was unaltered by cocaine exposure. The data suggest that 5-HT2 receptor-mediated responses for ACTH, corticosterone and prolactin secretion become supersensitive following repeated cocaine. In contrast, the 5-HT2 receptor-mediated response for oxytocin secretion is subsensitive. The cocaine-induced changes in postsynaptic 5-HT receptor function are likely a consequence of deficits in the function of 5-HT nerve terminals, that we have documented previously.
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PMID:Repeated cocaine modifies the neuroendocrine responses to the 5-HT1C/5-HT2 receptor agonist DOI. 133 68

Evidence suggests that activation of 5-HT1A receptors leads to inhibition of 5-HT2-mediated behavior. The purpose of this study was to investigate the interaction between 5-HT1A and 5-HT2 receptor-mediated hormone secretion. Rats were pretreated with the 5-HT1A agonists buspirone (0, 0.5, 2.0 mg/kg, i.p.), 8-OH-DPAT (0, 0.05, 0.2 mg/kg, s.c.) or ipsapirone (0, 1.0, 2.5 mg/kg, i.p.), 45 min before decapitation. The 5-HT2 agonist DOI was administered (0-10 mg/kg, i.p.) 15 min after injection of the 5-HT1A agonists. The three 5-HT1A agonists differentially altered the DOI-induced increase of concentrations of hormone in plasma. None of the three 5-HT1A agonists influenced the basal levels of renin, ACTH and prolactin but 8-OH-DPAT and buspirone increased the basal level of corticosterone in plasma. Also, 8-OH-DPAT increased the effects of DOI on the concentration of ACTH in plasma but ipsapirone and buspirone did not. None of the 5-HT1A agonists significantly affected DOI-induced increase of concentration of corticosterone in plasma. Buspirone and 8-OH-DPAT potentiated the effect of DOI on prolactin in plasma, but ipsapirone did not. Ipsapirone potentiated the effect of DOI on the concentration of renin in plasma but this effect was not observed in 8-OH-DPAT- and buspirone-pretreated rats. The results do not support the hypothesis for a functional interaction between 5-HT1A and 5-HT2 receptors, since the three 5-HT1A agonists did not have the same influence on the hormonal effects of DOI.
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PMID:Neuroendocrine responses to the serotonin2 agonist DOI are differentially modified by three 5-HT1A agonists. 135 39

We have investigated the effect of varying sodium intake on the renin-angiotensin system, ADP-induced platelet aggregation in vitro, and blood 5-HT concentrations in 9 male volunteers. Systolic blood pressure was slightly reduced during a low sodium diet, whereas the diastolic pressure remained unchanged. Plasma renin activity and aldosterone concentration both fell significantly when sodium intake was increased; plasma angiotensin II concentration also fell, but not significantly. There was a significant fall in haematocrit after an increased sodium intake, but there was no change in the whole-blood platelet count after correcting for this. There were no significant changes in either total (i.e. PRP) or platelet 5-HT concentrations. The extent of platelet aggregation induced by 5 and 20 mumol.l-1 of ADP increased significantly when dietary sodium intake was increased. When compared with low or normal sodium intakes, lower concentrations of ADP were required to produce 50% of maximum aggregation after a high sodium intake. The 5-HT2 receptor antagonist ketanserin (1 mumol.l-1 in vitro) reduced the extent of aggregation induced by 5 mumol.l-1 ADP after the volunteers had taken a high sodium diet, whereas the angiotensin II receptor antagonist saralasin (1 nmol.l-1) increased the rate of aggregation after the low sodium diet. Thus, during a high sodium intake, human platelets become more sensitive to the aggregating agent ADP. It is possible that this effect is mediated via platelet 5-HT2 receptors, since ketanserin abolished the increase in salt-induced aggregation seen with 5 mumol.l-1 ADP.
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PMID:The sensitivity of human blood platelets to the aggregating agent ADP during different dietary sodium intakes in healthy men. 149 45

Serotonergic drugs with 5-HT2 receptor agonist properties have been suggested to increase plasma vasopressin concentration, blood pressure (BP) and plasma renin activity (PRA). To study whether these actions are mediated by the same or different receptors, we used three potent 5-HT agonists with different structures and receptor binding profiles. All drugs were administered i.v. to conscious, unrestrained rats. The selective agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), which has high affinity for 5-HT2 receptors, caused marked increases in BP and PRA but no change in plasma vasopressin concentrations. The 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), which also binds to other 5-HT receptors, caused moderate increases in BP and PRA and significantly elevated plasma vasopressin concentrations. The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), did not increase any of these parameters. BP and PRA elevations paralleled each other after all drugs, while vasopressin responses were clearly different. Vasopressin responses to m-CPP were entirely antagonised by the 5-HT1/5-HT2 antagonist metergoline, partially by the 5-HT2/5-HT1C antagonists ritanserin and LY 53857, but not by the 5-HT2 antagonist ketanserin. Ritanserin, LY53857 and ketanserin all very effectively blocked BP responses to m-CPP. These findings suggest that BP and PRA but not vasopressin responses are mediated by 5-HT2 receptors. Vasopressin secretion is mediated by 5-HT1 receptors, most likely by 5-HT1C receptors.
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PMID:Pharmacological characterization of serotonin receptor subtypes involved in vasopressin and plasma renin activity responses to serotonin agonists. 153 17

The antihypertensive effects of intravenous injection of ketanserin, a 5-HT2 receptor antagonist, were assessed in conscious rabbits. In intact rabbits, ketanserin lowered blood pressure in a dose-dependent manner. The antihypertensive effects of ketanserin were also observed in rabbits with two-kidney, one clip (2K1C) hypertension and with one-kidney, one clip (1K1C) hypertension. The effect was more marked in the 1K1C rabbits with low plasma renin activity (PRA) and high plasma norepinephrine (PNE) than in 2K1C rabbits with high PRA and normal PNE. The heart rate was not changed. Ketanserin suppressed the pressor response to exogenous norepinephrine (0.6 micrograms/Kg) 15, 30 and 45 min after the injection of ketanserin (1 mg/Kg). It also suppressed the pressor response to phenylephrine (3 micrograms/Kg) 15 min after the injection, but it did not suppress the pressor response to angiotensin II (0.15 micrograms/Kg). In order to investigate baroreceptor function, balloons were placed around the abdominal aorta and the inferior vena cava and inflated alternately. Thus, the mean arterial pressure vs heart period-logistic curve was obtained under steady-state conditions. There were no changes after the drug administration in the range of heart period and the gain (the slope at midpoint of the curve). These results suggest that the inhibition of pressor response of norepinephrine has effects in addition to a direct vasodilatory action and that an alteration of baroreceptor function is not involved in the antihypertensive effects of ketanserin.
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PMID:Cardiovascular effects of ketanserin in conscious rabbits. 294 1

The role of endogenous 5-hydroxytryptamine (5-HT) in the control of blood pressure, the renin-angiotensin system and sympatho-adrenal function was investigated in normal man. Ketanserin (a specific 5-HT2 antagonist) administered intravenously caused a small decrease in blood pressure in salt-depleted recumbent subjects. A more marked postural fall in pressure occurred in both sodium-depleted and repleted normal subjects. Plasma active renin concentration and angiotensin II increased after administration of ketanserin, but plasma aldosterone, cortisol and noradrenaline were unchanged. 5-HT may be important in the control of blood pressure in man and specific 5-HT2 receptor antagonists could be a useful new class of antihypertensive agents.
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PMID:The effect of a 5-HT antagonist, ketanserin, on blood pressure, the renin-angiotensin system and sympathoadrenal function in normal man. 662 23

The new selective 5-HT2 receptor blocking agent ketanserin was given in a dose of 10 mg intravenously to 12 patients with essential hypertension. It caused a distinct fall in supine systemic arterial, right atrial, pulmonary artery, and pulmonary capillary "wedge" pressures. Cardiac output, renal blood flow, and glomerular filtration rate showed no persistent changes. Thus 5-HT2 receptor blockade caused dilatation of both resistance and capacitance vessels and of the renal vascular bed. Heart rate and plasma concentrations of renin and noradrenaline rose after ketanserin. These data suggest that 5-HT may have a role in maintaining high blood pressure.
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PMID:Treatment of hypertension with ketanserin, a new selective 5-HT2 receptor antagonist. 680 May 33

Mean arterial blood pressure (MAP), heart rate (HR) and arterial plasma levels of corticotropin (ACTH), renin activity (PRA) and catechols [norepinephrine (NE), epinephrine (EPI), and the intraneuronal NE metabolite dihydroxyphenylglycol (DHPG)] at baseline and in response to the serotonin-1C/2 (5-HT1C/5-HT2) agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI, 1.0 mg/kg i.a.) in conscious, freely-moving, juvenile (4 week old) spontaneously hypertensive rats (SHR's) and age-matched Wistar-Kyoto (WKY) normotensive control rats were measured simultaneously. Baseline levels of MAP, NE, DHPG, and EPI all were significantly higher in the SHR's. There was a similar trend for PRA, but ACTH did not differ between the two strains. DOI produced marked increases in levels of MAP, ACTH, EPI, and also PRA but did not affect NE or DHPG concentrations. HR decreased only in the WKY group after administration of DOI. The magnitudes of the EPI and ACTH responses did not differ between the rat strains. Responses of MAP and PRA were significantly larger in SHR's. These results suggest that there is a selective hyperresponsiveness of PRA and blood pressure to 5-HT2 receptor stimulation parallel to a deficient baroreceptor reflex in juvenile SHR's.
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PMID:Plasma catecholamine, renin activity, and ACTH responses to the serotonin receptor agonist DOI in juvenile spontaneously hypertensive rats. 823 34

Various childhood mood disorders are being treated with serotonin selective reuptake inhibitors (SSRIs) such as fluoxetine (Prozac(R)), yet limited data are available on their effects on serotonergic systems prior to maturation. This study investigated the effects of chronic fluoxetine treatment on 5-HT2A serotonin receptor-mediated neuroendocrine responses in young male rats. Prepubescent male rats were treated with saline or fluoxetine (10 mg/kg/day, i.p.) for 14 days, a treatment regimen producing maximal changes in postsynaptic 5-HT2A function in adults. Eighteen hours post-treatment, the rats received saline or increasing doses (0.5, 2.0, or 5.0 mg/kg, i.p.) of the 5-HT2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl ((+/-)-DOI). Trunk blood was obtained to determine changes in oxytocin, ACTH, corticosterone, and renin responses. Fluoxetine produced a small ( approximately 6%) but significant reduction in body weight gain, but no changes were observed in basal hormone levels. In both saline- and fluoxetine-treated rats, (+/-)-DOI increased plasma oxytocin levels in a dose-dependent manner. However, the magnitude of the oxytocin responses to all doses of (+/-)-DOI were markedly attenuated ( approximately 50%) in the fluoxetine-treated rats, indicating a functional reduction in the E(max) of 5-HT(2A) receptor-mediated oxytocin responses. In contrast, fluoxetine did not alter the (+/-)-DOI-induced increases in plasma ACTH, corticosterone, or renin. These data provide the first demonstration of selective neuroadaptive responses in 55-HT2A serotonin receptor function due to prepubescent treatment with fluoxetine. These data may be clinically relevant with respect to the use of selective serotonin reuptake inhibitors in children and adolescents.
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PMID:Fluoxetine treatment of prepubescent rats produces a selective functional reduction in the 5-HT2A receptor-mediated stimulation of oxytocin. 1608 47