Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of epinine or dopamine (both 1-10 micrograms kg-1 min-1) on systemic haemodynamics and plasma concentrations of catecholamines and prolactin were studied in conscious pigs before and after combined non-selective alpha- and beta-adrenoceptor blockade. 2. The plasma concentrations of the two compounds did not differ from each other over the entire dose-range. 3. Epinine increased aortic blood flow (AoBF, 24 +/- 6%), which was due to an increase in heart rate (HR) for doses less than 10 micrograms kg-1 min-1. At 10 micrograms kg-1 min-1, HR decreased slightly (10 +/- 3%, as compared to the value obtained at 5 micrograms kg-1 min-1) and stroke volume increased up to 15% (P < 0.05). Mean arterial pressure (MAP, 99 +/- 3 mmHg at baseline) decreased dose-dependently (14 +/- 2%, P < 0.05) up to the infusion rate of 5 micrograms kg-1 min-1, but increased by 4.0 +/- 1.8 mmHg during infusion of 10 micrograms kg-1 min-1. Systemic vascular resistance (SVR) decreased up to 23 +/- 3% for doses less than 10 micrograms kg-1 min-1, but did not change further during infusion of the highest dose. LVdP/dtmax increased during the two highest infusion rates up to 22 +/- 6% (P < 0.05). After the infusion was stopped there was an abrupt increase in HR (18 +/- 4%, P < 0.05) and a further decrease in SVR before all parameters returned to baseline.4. Dopamine caused increases in AoBF (27 +/- 3%) similar to epinine, the only difference being that HR continued to increase (32 +/- 5%) and MAP (13 +/- 3%) and SVR continued to decrease (31 +/- 3%) over the entire dose-range. The increase in LVdP/dt,,,, at the highest dose (48 +/- 4%, P <0.05) was more pronounced than with epinine.5. Adrenoceptor blockade inhibited all epinine-induced changes, but did not affect the dopamineinduced changes in AoBF, SVR and MAP, but attenuated the increases in HR and LVdP/dtmax.6. Noradrenaline (NA) and adrenaline (Ad) concentrations did not change during infusion of epinine or dopamine, but NA increased by 50% within 2.5 min after stopping the infusion of epinine. After adrenoceptor blockade NA and Ad concentrations did not change during infusion of dopamine, which contrasted with a decrease of 55 +/- 5% (P<0.05) in NA during infusion of epinine.7. Prolactin concentrations decreased gradually from 480 +/- 40 pg ml-' to 270 +/- 50 pg ml1' (P<0.05) during infusion of epinine, but did not change significantly during dopamine infusion.8. The differential effects of epinine and dopamine on MAP, SVR, plasma NA (before and after adrenoceptor blockade) and prolactin, leads us to conclude that in conscious pigs, epinine is a more potent a, P2 and D2-receptor agonist, but a weaker D,-receptor agonist than dopamine.
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PMID:Differential cardiovascular and neuroendocrine effects of epinine and dopamine in conscious pigs before and after adrenoceptor blockade. 133 Jan 72

Recent work suggests that hypophysectomized (HYPOX) rats show low levels of atrial natriuretic factor (ANF) and an attenuated diuresis and natriuresis to blood volume expansion. The purpose of this was (i) to examine the effect of various hormone replacements on ANF and renal excretion in HYPOX rats and (ii) to compare the renal responses to exogenous ANF in intact and HYPOX rats. Groups of rats received subcutaneous pellet implant of either dexamethasone (DEX), thyroxine (T4), or a placebo. Approximately 1 week later, they were anesthetized and subjected to a 20% blood volume expansion. DEX rats had a higher mean arterial pressure than placebo-treated rats while both MAP and heart rate were higher in T4 rats. Only the DEX rat showed augmented renal responses to volume expansion while no group showed significant changes in plasma ANF concentration during volume expansion. In a second series, groups of HYPOX rats received renal capsular transplants of either six hemi-pituitaries or six pieces of muscle which markedly raised serum prolactin levels in the hemi-pituitary group. The hemi-pituitary rats showed a greater diuresis and natriuresis during volume expansion than the muscle group and also showed a transient increase in plasma ANF. In addition, groups of either intact or HYPOX rats were anesthetized and received intravenous bolus injections of ANF. Both intact and HYPOX rats showed a very similar diuresis and natriuresis to exogenous ANF. However, potassium excretion was markedly reduced in HYPOX rats. The results show that DEX augments the renal responses to volume expansion by some mechanism which does not involve changes in plasma ANF. Thyroxine increases mean arterial pressure and heart rate in HYPOX rats but does not augment the renal or ANF responses to volume expansion. Chronic elevations in prolactin increase the renal response to volume expansion. Finally, the kidneys of HYPOX rats are capable of increasing sodium and water output in response to large doses of exogenous ANF.
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PMID:Studies on the role of the pituitary in the control of atrial natriuretic factor secretion and sodium excretion. 214 22

This prospective trial was designed to help in selecting therapy for patients with elevated and normal plasma prolactin. Ninety-two patients entered this trial, of whom 86 were evaluable for final analysis. Hyperprolactinemic patients (n = 31) were randomized to receive VAC/FMC chemotherapy with or without bromoergocryptine. Normoprolactinemic patients with 'low risk' metastatic disease (disease-free interval greater than 30 months, ER/PR positive or unknown) were treated with medroxyprogesterone acetate or VAC/FMC chemotherapy. Normoprolactinemic 'high risk' patients (n = 42) (disease-free interval less than 30 months, EP/PR negative) received VAC/FMC chemotherapy with or without medroxyprogesterone acetate (MAP). The results show that bromoergocryptine does not improve response rate, duration of response and survival. Median survival of patients with elevated basal plasma prolactin (greater than 15 ng/ml) is reduced to 9 months compared to patients with normal basal plasma prolactin (17 months, log-rank p = 0.005). Unexpectedly, TRH stimulation proved inappropriate to separate normo- and hyperprolactinemic patients in terms of survival. Normoprolactinemic 'low risks' (tamoxifen failures) were observed to qualify for further hormone therapy (median survival 21+ months). Normoprolactinemic 'high risks' showed median survival of about 12 months with no apparent benefit for those receiving MAP, additionally. The results suggest that basal hyperprolactinemia, disease free interval, ER/PR receptor status, and liver metastasis are important prognostic variables. Endocrine and cytotoxic chemotherapy should be selected according to these risk factors.
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PMID:Prospective randomized trial concerning hyper- and normoprolactinemia and the use of bromoergocryptine in patients with metastatic breast cancer. 295 Mar 59

For anesthesia, ataranalgesic combinations of benzodiazepines and ketamine have been reported to be advantageous alternatives to inhalation agents or high-dose opioids. In this study, the influence of midazolam-ketamine-N2O/O2 anesthesia on the endocrine metabolic response of patients during the course of reconstructive orthopedic surgery (n = 8) was investigated. METHODS. The dosage of anesthetic agents was calculated according to body weight. Thus, the amount of ketamine given in young adults (mean age = 24.1 years) was 30 micrograms/kg per minute. Pre-, intra-, and postoperatively, each of following hormones was measured by either radioimmunoassay or radioenzyme-linked assay: ACTH, aldosterone, cortisol, 17-dehydroepiandrosterone (17-DHEA), prolactin, insulin, T3, T4, thyroxine-binding globulin (TGB), epinephrine, norepinephrine, and dopamine. Additionally, the metabolites glucose, lactate, and free glycerin were measured perioperatively. RESULTS and CONCLUSION. The circulation remained relatively stable under midazolam-ketamine-N2O/O2 anesthesia (MAP +23%; HR +17%). ACTH secretion and prolactin secretion showed a significant rise (p less than 0.01) even before skin incision (Figs. 1, 3). A significant rise in cortisol levels occurred intraoperatively (+80%; p less than 0.01). Secretion of aldosterone (+246%; p less than 0.05) and 17-DHEA (+49%; p less than 0.05) essentially followed the secretory profile of cortisol, while insulin secretion did not rise significantly under acute surgical stress (Fig. 4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Combined midazolam-ketamine anesthesia in traumatologic interventions. Patterns of endocrine reactions]. 340 94

Based upon preliminary observations that tumor response to MPA was correlated to cortisol suppression 42 patients were treated with MPA at different dose levels. 1500 mg MPA p.o. almost completely suppressed endogenous cortisol production in 23 out of 23 patients. Consequently, 51 patients with advanced stage metastatic breast cancer were treated with Medroxyprogesteroneacetate (HD-MAP) at a dosage of 1500 mg p.o. daily or 500 mg i.m. on 5 days per week. There were 5 complete and 7 partical remissions, 23 patients with no change and 10 with progressive disease. 7 patients were not evaluable. Clinical results correlated to plasma cortisol and prolactin blood levels bot not to LH, FSH, TSH, TBI, T3, T4, ACTH and aldosterone measurements. There was no patient with relapse and suppressed cortisol or normal prolactin measurements. The development of pituituary resistance to MPA is suggested. HD-MPA was equally effective in estrogen and/or progesterone receptor positive as in receptor negative patients. It is proposed that cortisol and prolactin determinations are useful to monitor for effective MPA treatment and the early detection of MPA resistance.
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PMID:[High dose medroxyprogesteroneacetate in metastasizing breast cancer: correlations between course of the disease and hormone profiles]. 622 46

Evidence has been accumulated implicating sex hormones as possible modulators of extrapyramidal motor function. In the present study we have investigated the effects of estrogens, progesterone, testosterone, prolactin and calcitonin on behavioral parameters related to nigro-striatal dopaminergic system, such as haloperidol-induced catalepsy in male rats. It was found that 7-days estradiol benzoate treatment (5 micrograms/rat/day) significantly increases haloperidol-induced catalepsy, suggesting a possible antidopaminergic activity of estrogens. On the other hand, prolactin facilitates nigro-striatal dopaminergic transmission. Interestingly, 7 day treatment with medroxy-acetate progesterone (MAP, 5 mg/Kg, i.p.) brings about a trend to a decrease in haloperidol-induced catalepsy, while no significantly effect was observed following acute MAP administration at the same dose. So, it is tempting to speculate that chronic progestinic treatment may result in an increase in dopaminergic tonus. Testosterone, acutely administered (5mg/kg.s.c.) induces changes similar to those observed following progesterone administration. Finally, also calcitonin is able to influence haloperidol-induced catalepsy by markedly increasing it.
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PMID:[Neuroendocrine modulation of haloperidol-induced catalepsy]. 630 68

Effects of the GABAergic drug diazepam (0.15 mg kg-1, i.v.) on cardiovascular and endocrine responses to 50 degrees head-up tilt were evaluated in seven men. During the initial phase of tilt (normotensive phase), increases in heart rate (HR) and total peripheral resistance (TPR) and decreases in cardiac output were unaffected by diazepam. Also the associated increase in plasma noradrenaline did not change, while response in plasma ACTH was diminished and in plasma cortisol abolished by diazepam (F(1,10) = 6.45; P < 0.03). After 42 +/- 4 min of sustained tilt with saline (control) and 47 +/- 6 min (n.s.) after diazepam, presyncopal symptoms appeared (hypotensive phase) associated with decreases in HR, MAP, and TPR (P < 0.01). This episode induced a 2-3-fold increase in plasma ACTH, beta-endorphin, prolactin, cortisol (< 0.01), and a moderate increase in plasma adrenaline (P < 0.05). Diazepam did not significantly change cardiovascular and endocrine responses to the hypotensive phase of tilt. Results indicate that diazepam attenuates the cortisol part of pituitary-adrenal responses to moderate, but not to severe, central hypovolaemia in humans with no effect on cardiovascular tolerance.
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PMID:Effect of diazepam on endocrine and cardiovascular responses to head-up tilt in humans. 835 26

We have assessed the potential for myocardial ischaemia during laparoscopic cholecystectomy in 16 otherwise healthy patients. Continuous ambulatory ECG monitoring was commenced 12 h before operation and continued for 24 h after operation. The neuroendocrine stress response was assessed by measuring plasma concentrations of adrenaline and noradrenaline, human growth hormone, cortisol, renin and aldosterone, and prolactin, at specified times during surgery. Acute ST segment changes in the ECG occurred in only two patients. These episodes were independent of creation of pneumoperitoneum and changes in position. Acute intraoperative increases in MAP were noted during insufflation of carbon dioxide and reverse Trendelenburg positioning (P < 0.05). A four-fold increase in plasma concentrations of renin and aldosterone was noted after pneumoperitoneum and reverse Trendelenburg positioning (P > 0.05). There was a linear correlation between changes in plasma renin and aldosterone concentrations and MAP (r = 0.97 and r = 0.85, respectively). Prolactin concentrations increased four-fold after induction of anaesthesia. Cortisol, HGH, adrenaline and noradrenaline concentrations increased after deflation of the pneumoperitoneum. The time profile-concentration changes of increased MAP and renin-aldosterone suggests a cause-effect relationship. Increased intra-abdominal pressure and reverse Trendelenburg positioning may reduce cardiac output and renal blood flow. The early increase in prolactin concentration was probably secondary to the effect of the opioid fentanyl.
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PMID:Laparoscopic cholecystectomy: haemodynamic and neuroendocrine responses after pneumoperitoneum and changes in position. 901 45

Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of ETs and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive ETs are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ETA and ETB receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ETA receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca(2+)-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+]i that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca(2+)- mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D-and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that ETs participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells.
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PMID:Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. 881 99

The MAP kinase pathway has been shown to be active in many growth factor signaling systems, including that of prolactin (PRL). In our studies, the main objective was to examine the possible involvement of MEK kinases (Map/Erk kinase kinases) in PRL-stimulated mitogenic and lactogenic processes. We used the MEK kinase inhibitor PD 098059 to block MEK kinase activation in the Nb2 cell line and mammary gland explants derived from 12- to 14-day pregnancy mice. PD 098059 attenuated PRL-induced Nb2 cell mitogenesis at 10 microM and a maximum inhibition was observed at 100 microM. In cultured mammary tissues, PD 098059 at 100 microM had no effect on the PRL stimulation of lipid, casein and lactose synthesis and iodide uptake. Further, the growth-inhibitory effect of PD 098059 on Nb2 cells was ameliorated when the drug was removed from the culture medium, indicating that PD 098059 acts in a reversible manner. When MEK1 was immunoprecipitated from PD 098059 and/or PRL treated Nb2 cells, PRL-stimulated MEK1 kinase activity was directly inhibited by PD 098059 at concentrations employed in the culture experiments. PRL has no effect on the tyrosyl phosphorylation of MAP kinases in cultured mammary tissues derived from pregnant mice, whereas earlier we found that PRL stimulates the tyrosyl phosphorylation of all four MAP kinases in Nb2 cells. The results suggest that the MAP kinase pathway plays an important role in the PRL stimulation of Nb2 cell mitogenesis but is not involved in the PRL stimulation of milk product synthesis.
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PMID:The MEK inhibitor PD 098059 inhibits prolactin-induced Nb2 cell mitogenesis but not milk product synthesis in cultured mouse mammary tissues. 982 84


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