Demonstration of an inwardly rectifying K+ current component modulated by thyrotropin-releasing hormone and caffeine in GH3 rat anterior pituitary cells

 Reduction of an inwardly rectifying K⁺ current by thyrotropin-releasing hormone (TRH) and caffeine has been considered to be an important determinant of electrical activity increases in GH₃ rat anterior pituitary cells. However, the existence of an inwardly rectifying K⁺ current component was recently regarded as a misidentification of an M-like outward current, proposed to be the TRH target in pituitary cells, including GH₃ cells. In this report, an inwardly rectifying component of K⁺ current is indeed demonstrated in perforated-patch voltage-clamped GH₃ cells. The degree of rectification varied from cell to cell, but both TRH and caffeine specifically blocked a fraction of current with strong rectification in the hyperpolarizing direction. Use of ramp pulses to continuously modify the membrane potential demonstrated a prominent blockade even in cells with no current reduction at voltages at which M-currents are active. Depolarization steps to positive voltages at the maximum of the inward current induced a caffeine-sensitive instantaneous outward current followed by a single exponential decay. The magnitude of this current was modified in a biphasic way according to the duration of the previous hyperpolarization step. The kinetic characteristics of the current are compatible with the possibility that removal from inactivation of a fast-inactivating delayed rectifier causes the hyperpolarization-induced current. Furthermore, the inwardly rectifying current was blocked by astemizole, a potent and selective inhibitor of human ether-á-go-go -related gene (HERG) K⁺ channels. Along with other pharmacological and kinetic evidence, this indicates that the secretagogue-regulated current is probably mediated by a HERG-like K⁺ channel. Addition of astemizole to current-clamped cells induced clear increases in the frequency of action potential production. Thus, an inwardly-rectifying K⁺ current and not an M-like outward current seems to be involved in TRH and caffeine modulation of electrical activity in GH₃ cells. Received: 15 May 1997 / Received after revision and accepted: 24 July 1997     

Atrial natriuretic peptide in human urine

Summary A highly sensitive radioimmunoassay to measure atrial natriuretic peptide (ANP) concentration in urine has been established, and its clinical usefulness is presented. ANP in urine was stable at 4° C for several days and was easily measured by our radioimmunoassay. The average ANP excretion in 65 healthy persons was 25.0±1.4 ng/day (mean ± SEM) and the fractional excretion of ANP was 0.7±0.05%. In 14 patients with congestive heart failure, the average ANP excretion was 119.2±29.4 ng/day, which decreased to 53.3±11.0 after successful treatment.Abbreviations ANP atrial natriuretic peptide - hANP human atrial natriuretic peptide - RIA radioimmunoasay - NSB non specific bound - FE_ANP the fractional excretion of atrial natriuretic peptide - FE_Na the fractional excretion of sodium - SIADH the syngrome of inappropriate secretion of antidiuretic hormone     

Neuropeptides TRH and cyclo(His-Pro) share neuromodulatory,but not stimulatory,action on hypothalamic neurons in vitro: implication for the regulation of feeding

Summary Electrical activity of neurons in rat hypothalamic ventromedial nucleus was recorded in tissue slices, to investigate central neural mechanisms underlying reduction of food intake caused by TRH and its metabolite, cyclo(His-Pro) [cHP]. Application of TRH had two actions: stimulation of neuronal activity, which was desensitized on closely repeated applications; and modulation of neuronal responses to neurotransmitters, even in the absence of the stimulatory action. The neuromodulatory but not the direct stimulatory action could also be achieved by cHP. The neuromodulatory action is more likely to be a neural mechanism underlying the inhibition of feeding, while other biological functions, unique to TRH, may depend on direct stimulation. In this way, TRH could achieve different biological results through different modes of action on hypothalamic neurons.     

Regulation of growth hormone during exercise by oxygen demand and availability

Summary Five normal men performed seven sets of seven squats at a load equal to 80% of their seven repetition maximum. Plasma growth hormone (GH) and lactate levels increased during and after the completion of the exercise. A significant (r=0.93, P<0.001) linear correlation was found between GH changes and the corresponding oxygen Demand/Availability (D/A) ratio expressed by (where f=[lactate at time x]/[lactate at time 0]). A retrospective examination of previously published data from our laboratory and others also demonstrated the existence of a significant correlation between changes in plasma GH levels and the D/A ratios over a wide variety of exercise; aerobic and anaerobic, continuous and intermittent, weight lifting and cycling, in both fit and unfit subjects under normoxic and hypoxic conditions. It is suggested that the balance between oxygen demand and availability may be an important regulator of GH secretion during exercise. DCIEM No. 87-P-27     

Anti-T-cell strategies in the treatment of allergic disease

Specific allergen immunotherapy (SIT) has been shown to be effective in modulating allergic responses in diseases such as rhinitis and asthma. However, the ability of whole allergen to cross link mast cell bound IgE, resulting in release of mediators such as histamine, has limited the application of this therapy to carefully selected patients who have failed conventional pharmacotherapy. The use of peptide sequences corresponding to T cell epitopes of the allergen has been postulated as an alternative to SIT in which high molar doses of T cell epitope can be delivered over a shorter time period and with improved safety. Using peptides from the sequence of the major cat allergen, Fel d 1, we have demonstrated the ability to induce transient T cell activation, resulting in isolated late asthmatic reactions, which are followed by prolonged periods of allergen-specific hyporesponsiveness, both to peptide re-challenge and to cutaneous challenge with whole allergen. Thus, peptide therapy may prove safe and efficacious in the treatment of allergic diseases.     

Concordant and discordant effects on cardiovascular risks exerted by oestrogen and progestogen in women using oral contraception and hormone replacement therapy. ESHRE Capri Workshop Group

The major indications for the clinical use of oestrogen and progestogen are oral contraception (OC) in young women, and hormonal replacement therapy (HRT) in menopause. Over the past few years, epidemiological data have associated the use of these hormones to different cardiovascular conditions such as myocardial infarction, cerebrovascular disease and venous thromboembolism. This review summarizes the data discussed and the conclusions achieved by the ESHRE Capri Workshop Group, recently published in Human Reproduction.     

Growth hormone as an early embryonic growth and differentiation factor

In this review we consider the evidence that growth hormone (GH) acts in the embryo as a local growth, differentiation, and cell survival factor. Because both GH and its receptors are present in the early embryo before the functional differentiation of pituitary somatotrophs and before the establishment of a functioning circulatory system, the conditions are such that GH may be a member of the large battery of autocrine/paracrine growth factors that control embryonic development. It has been clearly established that GH is able to exert direct effects, independent of insulin-like growth factor-I (IGF-I), on the differentiation, proliferation, and survival of cells in a wide variety of tissues in the embryo, fetus, and adult. The signaling pathways behind these effects of GH are now beginning to be determined, establishing early extrapituitary GH as a bona fide developmental growth factor.     

Proctolin-related material in the mouse brain as revealed by immunohistochemistry

By use of a specific antiserum against the insect peptide proctolin we were able to identify proctolin-immunoreactive neurons in the mouse brain. These nerve cells belong to the nuc. mesencephalicus n. trigemini. Furthermore, the antiserum stained very few nerve fibers with varicosities in the immediate neighborhood of the roof of the third ventricle. The chemical identity of the immunoreactive material with genuine proctolin remains to be elucidated.     

Mevalonic acidemia: First case of Japan

Summary Mevalonic acidemia is a rare metabolic disorder due to mevalonate kinase deficiency which affects the biosynthesis of cholesterol and nonsterol isoprenes. We report the first case of Japan. The clinical course is characterized by intrauterine growth retardation, postnatal growth failure, intractable diarrhea, liver dysfunctions and death at three months of age. Dysmorphic features including triangular face, protrusion of forehead, hypertelorism, low set ears and micrognathism were noted. High mevalonic acid level was found by GC/MS.     

Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides

1. Download : Download high-res image (202KB)
2. Download : Download full-size image