INTERACTION BETWEEN EPIDERMAL GROWTH FACTOR AND ARGININE VASOPRESSIN IN RENAL MEDULLARY MEMBRANES

1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin-induced water reabsorption. 2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subtypes. 3. Radioligand binding displacement assays demonstrated that although arginine vasopressin related peptides displaced both radioligands from renal medullary membranes at low concentrations epidermal growth factor displaced neither. 4. Arginine vasopressin V2 receptor second messenger cyclic adenosine monophosphate (CAMP) production was inhibited by epidermal growth factor (IC₅₀ 2 ± 10^?7 mol/L) as was sodium fluoride cAMP production but only at much higher concentrations. 5. Therefore the diuretic effect of epidermal growth factor is not via direct antagonism of arginine vasopressin receptors but seems mediated via inhibition of the V2 second messenger system.     

The Recognition of Hypothalamo-Neurohypophysial Functions by Developing T Cells

Neuropeptide signals and specific neuropeptide receptors have been described in the thymus supporting the concept of a close dialogue between the neuroendocrine and the immune systems at the level of early T-cell differentiation. In this paper, we review recent data about neurohypophysial (NHP)-related peptides detected in the thymus from different species. We suggest that we are dealing in fact with other member(s) of the NHP hormone family, which seems to exert its activity locally through a novel model of cell-to-cell signaling, that of cryptocrine communication. This model involves exchange of signals between thymic epithelial cells and developing thymocytes. The NHP-related peptides have been shown to trigger thymocyte proliferation and could induce immune tolerance of this highly conserved neuroendocrine family.     

健康人加压素释放和渴感的渗透压阈值

报道１２名受试者在静滴５％ＮａＣｌ２ｈ（每分钟０．０６ｍｌ／ｋｇ）的过程中血钠、血渗、血浆精氨酸加压素（ＡＶＰ）浓度和渴感等级的变化。结果显示，血浆ＡＶＰ浓度及渴感等级分别与血渗呈线性相关，回归方程分别为：血浆ＡＶＰ浓度（ｐＡＶＰ）－０．２４［血浆渗透压（ｐＯｓｍ）－２７４］（ｒ＝０．７２，Ｐ＜０．００１）；渴感等级（Ｔｈ）＝０．２３（ｐＯｓｍ－２７９）（ｒ＝０．６２，Ｐ＜０．００１）．两者灵敏度及阈值均较国外文献报道的结果低，认为加压素释放及渴感的渗透压阈值可能与遗传因素及生活习俗有关，ＡＶＰ分泌及渴感的渗透压调节可能存在种族差异。     

NIFEDIPINE BLOCKS ACTH AND CORTISOL RELEASE IN MAN

1. The present study investigated the effect of prior administration of nifedipine on AVP-induced ACTH release in seven normal volunteers. Three protocols were used: 20 mg oral nifedipine; 0.14 pressor units intramuscular (i.m.) per kg bodyweight aqueous AVP; oral nifedipine plus i.m. AVP 90 min later. Plasma ACTH and cortisol were measured at intervals for 2.5 h during each test. 2. The mean peak plasma ACTH and cortisol levels and the mean peak changes from basal in these levels were significantly lower in the nifedipine/AVP test than in the AVP alone test. The integrated area under the cortisol time curve was significantly lower for the nifedipine/AVP test than that for the AVP test alone. Nifedipine alone caused no changes in ACTH or cortisol. 3. Acute administration of oral nifedipine caused an inhibition of AVP-stimulated ACTH and cortisol release in normal humans. This effect may be due to blockade of plasma membrane calcium channels normally activated during AVP stimulation of pituitary corticotrophs.     

Raised intracranial pressure,the syndrome of inappropriate antidiuretic hormone secretion,and arginine vasopressin in tuberculous meningitis

Intracranial pressure (ICP) monitored shortly after admission over a period of 1 h in 31 children with tuberculous meningitis (TBM) was significantly higher (median 22.5 mm Hg, range 8.4–50.9 mmHg) in 19 children with laboratory evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) than in 12 children without such evidence (median 16.2 mmHg, range 5.8–42.5 mmHg; P = 0.027). Neither plasma nor cerebrospinal fluid arginine vasopressin (AVP) was related to ICP (r = 0.33 and 0.13 respectively). Mean arterial pressure (MAP) was measured in 23 children and a moderate correlation was found with plasma AVP (r = 0.62; P = 0.0019). In TBM, plasma AVP may be secreted as a response to raised ICP in an effort to raise MAP and maintain cerebral perfusion pressure. In this setting excess fluid may be inappropriately retained, leading to hyponatremia and hypo-osmolemia.     

Effects of arginine, S-adenosylmethionine and polyamines on nerve regeneration

Introduction - Axon growth and axon regeneration are complex processes requiring an adequate supply of certain metabolic precursors and nutrients. Material and methods - This article reviews the studies examining some of the processes of protein modification fundamental to both nerve regeneration and to the continuous and adequate supply of specific factors such as arginine, S-adenosylmethionine and polyamines. Results - The process of arginylation notably increases following nerve injury and during subsequent regeneration of the nerve, with the most likelyfunction of arginine-modification of nerve proteins being the degradation of proteins damaged through injury. It appears that defective methyl group metabolism may be one of the leading causes of demyelination, as suggested by the observation of reduced cerebrospinal fluid concentrations of s-adenosylmethionine (SAMe) and 5-methyltetrahydrofolate, the key metabolites in methylation processes, in patients with a reduction in myelination of corticospinal tracts. Polyamine synthesis, which depends strongly on the availability of both SAMe and arginine, markedly increases in neurons soon after an injury. This "polyamine-response" has been found to be essential for the survival ofthe parent neurons after injury to their axons. Polyamines probably exert their effects through involvement in DNA, RNA and protein synthesis, or through post-translational modifications that areindicated as the most relevant events of the "axon reaction." Conclusions - Nerve regeneration requires the presence of arginine, s-adenosylmethionine, and polyamines. Further studies are needed to explore the mechanisms involved in these processes.     

Plasma concentrations of prolactin, noradrenaline, vasopressin and oxytocin during and after a prolonged epileptic seizure

The time course and extent of changes in plasma prolactin, noradrenaline, vasopressin and oxytocin levels is reported following serial observations of a prolonged epileptic seizure arising in the temporal lobe, recorded by video-EEG-telemetry, in which the epileptic activity evolved from a simple partial to complex partial to secondarily generalised attack. The prolactin levels were markedly elevated during the phase of the simple partial seizure, at a time when consciousness was preserved, when motor activity was minimal and when EEG activity was highly localised. The hormonal levels continued to rise during the subsequent seizure evolution, suggesting that the duration (or intensity) of the seizure is an important, perhaps the most important, factor determining the degree of prolactin release during limbic seizures. Indeed, the prolactin elevation in this case (26 times the baseline level) is higher than any previously recorded, reflecting the unusual duration and intensity of this seizure. We did not observe the phenomenon of "exhaustion" of prolactin release and levels peaked after 49 min, and were high for over 2 h after the onset of the seizure, and after the convulsion had ceased. The concentrations of vasopressin, oxytocin and noradrenaline remained low during the aura, but rapidly increased during the phase of generalisation. The oxytocin and noradrenaline levels peaked during the phase of generalised convulsion, but the vasopressin levels peaked well into the post ictal phase, and remained high for several hours. The differing patterns of hormone release are likely to be related to the different anatomical sites of the hypothalamic perikarya, the relative importance of excitatory and inhibitory hypophysiotrophic agents in the release of anterior pituitary hormones and the localised release of neuromodulatory agents.     

ACUTE EFFECT OF ETHANOL ON RENAL ELECTROLYTE TRANSPORT IN THE RAT

1. Despite human and animal studies, the direct effect of ethanol on renal water and electrolyte transport is poorly understood. The acute effect of increasing plasma concentrations of ethanol was evaluated in a water diuretic anaesthetized rat model which inhibits endogenous arginine vaso-pressin (AVP) release. 2. Ethanol at a plasma concentration of 1.69 ±0.28 mmol/L produced an immediate increase in urine flow (174 ± 11 μL/min pre-ethanol and 189 ± 13 and then 206 ± 12 μL/min during the ethanol infusion; P<0.001) as well as an increase in fractional sodium excretion (0.17 ± 0.04 to 0.28 ± 0.05 and 0.27 ± 0.05%; P<0.001). There was also a brief phosphaturia. These increases in electrolyte excretion had returned to control values by 20 min despite a further increase in the plasma ethanol concentration. 3. The urinary excretion of potassium, calcium and magnesium was not altered nor was glomerular filtration rate or renal plasma flow. 4. Ethanol at a mean concentration of 1.60 mmol/L did not alter the action of a maximal concentration of AVP (75 ng/kg) on water or electrolyte transport. However, the antidiuretic effect of a submaximal concentration of AVP (7.5 ng/kg) was augmented by ethanol at concentrations of 1.63 and 0.98 mmol/L. 5. These studies suggest that the ethanol induced diuresis commonly ascribed to inhibition of AVP secretion may also be due to other intrarenal effects of ethanol, possibly acting within the proximal tubule. These results also confirm recent in vitro findings that while ethanol does not inhibit the action of a maximal concentration of AVP, it does modulate the effects of lower AVP concentrations.     

L-精氨酸对高原肺水肿患者血液流变学的作用

目的：探讨雾化吸入左旋精氨酸（L-Arg）对高原肺水肿患者血液流变学的影响。方法：在海拔3700m高原，采用氧气驱动雾化吸入L-Arg，治疗高原肺水肿（HAPE）患者9例（L-Arg组），将吸入低浓度一氧化氮（NO）混合气治疗的另外8例高原肺水肿患者（NO组）作对照，分别测定患者的红细胞压积（HCT）、血液粘度（ηb）、血浆粘度（ηp）、还原粘度（ηr）、红细胞刚性指数（IR）、红细胞变形系数（TK）、红细胞聚集系数（VAI）和血栓形成系数（TFL）等血液流变学指标。结果：NO组和L-Arg组治疗后较治愈前ηb、ηp、ηr、VAI、TFL均降低显著（P〈0．05～0．01），而HCT、TK、IR无统计学差异（P〉0．05）；NO组与L-Arg组比较，各指标均无统计学差异（P〉0．01）。结论：L-Arg治疗HAPE有效，通过提高NO水平而改善血液循环，且经济简便，易于推广应用。     

Age-Dependent Accumulation of Hybrid Vasopressin-Oxytocin Gene Products but not Hybrid Oxytocin-Vasopressin Products in the Endoplasmic Reticulum of Brattleboro Rats

The age-dependence of the incidence of magnocellular neurosecretory neurons containing abnormal accumulations of peptide in the rough endoplasmic reticulum was examined in homozygous Brattleboro rats and in their wild-type Long Evans counterparts. Neurons in which the immunophenotype of the peptide aggregates indicate that somatic cross-over mutations involving the 5' end of the vasopressin gene and the 3' end of the oxytocin gene have occurred, increased with age in homozygous Brattleboro rats, reaching a maximum of 24 cells per hypothalamus (approximately 0.6% of the vasopressin neurons). The increase occurred in both male and female animals but was significantly greater in females. The average incidence of such cells was 6 times greater in the supraoptic than in the paraventricular nucleus. No such cells could be detected in either nucleus of Long Evans rats despite the evidence for hybrid mRNA in these animals. Moreover, no accumulation of peptide translated from the hybrid mRNAs derived from the 5' end of the oxytocin gene and the 3' end of the vasopressin gene could be detected in either Brattleboro or Long Evans animals. These results strongly suggest that the accumulation of peptide in the rough endoplasmic reticulum of vasopressin neurons in homozygous Brattleboro rats is due to an abnormality other than the somatic crossing-over mutation. A second type of abnormal magnocellular neuron with accumulations of peptide in the rough endoplasmic reticulum, in which the immunophenotype of the peptide reveals products derived only from the oxytocin precursor, was present in both Long Evans and Brattleboro rats, but did not increase with age in Brattleboro rats. The incidence of these cells was similar in the supraoptic and paraventricular nuclei.