摘要:

This minireview aims to discuss the new evidence for a multipurpose prohormone function for chromogranin A, the index member of the chromogranin/secretogranin family of universally distributed, uniquely acidic proteins.

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1994.tb09779.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Naturally occurring amino terminal fragments of chromogranin A (CGA), the calcium‐binding protein found in all endocrine secretory vesicles, have vasoinhibitory activity when tested in isolated segments of the endothelium‐denuded human saphenous vein. Synthetic peptides corresponding to sequences within the first 76 residues of chromogranin A have been made and tested for biological activity. Full length vasostatin I (CGA1–76) (40 nM), but not the truncated vasostatin I, CGA1–40(100 nM) mimics natural chromogranin A fragments in its inhibition of contractions induced by endothelin‐1 (ET‐1) in calcium containing medium. CGA1–40(100 nM) mimics the inhibitory effect of the vasostatins on the contractions induced in the absence of extracellular calcium by high potassium and noradrenaline, but not by ET‐1. The iodinated peptides both exhibit saturable binding in an aortic smooth muscle cell line, indicative of a single class of high affinity binding protein (‘receptor’ with an apparent KDof approximately 45 nM. This binding is not affected by endothelin‐1. Iodinated peptides can be crosslinked to a single polypeptide in binding experiments performed on intact calf aorti

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1994.tb09780.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The basic polypeptide aprotinin (Ap), mol. wt 6513, is freely filtered in glomeruli and completely reabsorbed by the proximal tubules. Cellular processing is slow with return to plasma of breakdown products beginning after 20–30 min. When corrected for Gibbs‐Donnan distribution of Ap between glomerular filtrate and plasma (i.e. 0.65 at a plasma protein concentration of 50 mg ml‐1), the renal clearance of [125I]Ap, estimated as the ratio of kidney uptake and integrated non‐protein bound plasma125I concentration, equals that of [61Cr]EDTA (urine + kidney content). Zonal GFR per gram tissue was obtained from uptake in three to six samples from outer and inner cortex (OC, IC) and the cortico‐medullary border zone, 5–30 min after i.v. injection in rats. Control GFR in OC was 2.05 (SD 0.39) ml g'1min1and the IC/OC ratio 0.66 (SD 0.14). Repeated local clearances (C, and C,) were obtained by injecting a second tracer (i.e. [131I]Ap) 15 min after the first injection (i.e. [125I]Ap), which by then had a low plasma concentration. The kidneys were removed at 30 min, frozen and dissected. During control conditions Cn/C, averaged 1.06 in OC and IC, and the coefficient of variation (CV) between CII/CIratios of individual tissue samples was 2% in both zones. Lowering left renal arterial pressure before the second injection reduced GFR proportionally in both zones (34 and 37%) with a CV of intersample C11/C11, ratios of 5%. We conclude that the method allows precise and repeatable measurements of local an

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1994.tb09781.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The basic polypeptide aprotinin (Ap), mol. wt 6500, pi 10.5, is filtered in the glomeruli, virtually completely taken up by the proximal tubular cells and retained there for many hours. This process was studied in rats by determining the renal plasma clearance (CAp) as the amount of [126I]Ap accumulated in the kidney plus that excreted in the urine per unit of time divided by the integrated plasma concentration. In periods lasting 4–20 min after i.v. bolus injection or infusion to constant plasma concentration, CApwas 65% of glomerular filtration rate (GFR) estimated as kidney plus urinary clearance of [51Cr]EDTA (CCr.EDTA). Less than 0.8% of the filtered Ap appeared in the urine. CApvaried inversely with plasma protein concentration in mgml“1: CAp/CCrEDTA= 0.98‐0.0058 × PPr, corresponding to a glomerular Gibbs‐Donnan distribution for a net molecular charge of + 6, in agreement with the amino acid composition of Ap. CAp(kidney + urinary) was not altered by inhibiting tubular uptake of [125I]Ap by maleate or by exceeding the uptake capacity with large doses of unlabelled Ap. Neutralized Ap (malonylated) did not accumulate in the kidney, but showed a urinary clearance indistinguishable from that of [51Cr]EDTA. Both CApand C(.rEDTAwere reduced to 0.04 ml min‐1when glomerular filtration pressure was lowered by ureteral stasis and increased PPr(80–90 mg ml”1). These findings indicate: (1) no steric or charge restriction to filtration of Ap in the glomerular membrane, (2) the Gibbs‐Donnan equilibrium should be considered when estimating glomerular sieving of charged polypeptides in intact animals (3) charge dependent tubular uptake, (4) little or no transtubular transport of intact Ap, (5) no appreciable tubular uptake of Ap from the peritubular side and (6) local renal accumulation of Ap in a period of up to 20 min may be used to estimate local glomerular filtration and/or local proximal tubular reabsorption rates.Model analysis based on the appearance of125I in plasma, the time course of renal Ap content, and literature data on subcellular Ap distribution are consistent with two populations of endosomes, transporting Ap at widely different rates from the proximal tubular brush border to the lysosomes where breakdown occur

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1994.tb09782.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Nephrotic syndrome was induced in seven rats by daily aminonucleoside injections. Experiments were performed in anaesthesia 6 or 7 d later when protein loss in urine had reduced serum colloid osmotic pressure (COP) to 8.2 ± 0.9 (SD) mmHg compared with 20.2 ± 2.2 mmHg in controls(P<0.01). Due to the decreased COP in the nephrotic rats, lymph flow in the main mesenteric lymphatic was 29.5 ± 11.5,;1 min‐1compared with 4.2 ±2.2.2μl min‐1in the control rats(P<0.01). The corresponding hyaluronan concentrations were 3.4 ± 0.9 μg ml‐1and 12.0 ± 3.5 μg ml‐1, respectively(P<0.01). Nevertheless lymphatic hyaluronan output was doubled in the nephrotic rats, but this did not affect the hyaluronan content of the small intestine of 192 ± 58μg‐1dry wt compared with 215±69 μg g‐1in controls(P ±0.05). During a 20 min intravenous 0.9% saline infusion of 4 ml 100 g‐lrat, the hyaluronan concentration increased to 18.3 (6.0) μg ml‐1in mesenteric lymph in controls, whereas the concentration in lymph from the nephrotic rats remained unchanged. Lymphatic output increased, however, in this group as well due to the elevated flow. The amount of hyaluronan cleared daily by the main mesenteric lymphatic in awake rats corresponds to about half the tissue hyaluronan content in the drained area (Østgaard&Reed 1993 b). The unaltered tissue content of hyaluronan in the nephrotic rats must therefore imply an increased production of hyaluronan in response to the increased interstitial washout of hyaluronan

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1994.tb09783.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The protein constituents of cat parotid saliva evoked by parasympathetic stimulation or the infusion of bethanechol have been compared by sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE). The SDS‐PAGE patterns were highly reproducible for an individual cat and revealed up to 30 polypeptide bands in microlitre volumes of unconcentrated saliva. Only minor and predominantly quantitative differences were detected in the salivary protein composition of different cats. SDS‐PAGE demonstrates quantitative rather than qualitative changes in the protein composition of saliva evoked in response to different stimuli. The latter included preliminary observations on the effect of vasoactive intestinal peptide (VIP) on the bethanechol‐evoked

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1994.tb09784.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Speed‐torque relations of the quadriceps femors muscle group were determined using eight healthy subjects. Isometric or isovelocity, shortening muscle actions were performed at 15 speeds (0–6.28 rad s‐1) and torque was measured 0.78 and 0.52 rad below horizontal. Unilateral actions were evoked by surface electrical stimulation or by maximal voluntary effort. Stimulation current evoked a torque equal to approx. 70% of maximal voluntary isometric and was held constant across speeds. For the voluntary or stimulation tests, torque decreased(P<0.05) with increasing speed. This response in relative terms was greater(P<0.05) for the stimulation than for the voluntary tests. The difference in the decline in relative torque for the simulation vs. voluntary tests was not influenced by the angle at which torque was measured, and thereby muscle length. Speed‐torque data for the two stimulation tests fit a linearized plot of a hyperbolic relation for the higher tests speeds. When torque was measured at the greater joint angle (0.78 rad), and thereby longer muscle length, the equation was Po – P/V = Po 0.724‐1.078 (p<0.05, r2= 0.95) for speeds greater than 0.70 rad s‐1. For the shorter muscle length, the equation for data collected at speeds greater than 1.13 rad s“1was Po‐P/V = Po 0.467 + 4.61 (P<0.05, r2= 0.91). Inclusion of data for the next slower speed markedly compromised the ‘fit’ for either linear relation. The results suggest that the extent of force limitation by ‘some neural inhibitory mechanism’ during maximal voluntary effort has previously been over‐estimated because the speed‐torque relation for the quadriceps femoris muscle group was not hyperbolic in nature at ‘slow’ speeds when involuntary, shortening actions were studied. The magnitude of force limitation does not, however,

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1994.tb09785.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The objective was to investigate electromyographic activity (EMG) and isometric force tremor (IFT) changes during a sustained sub‐maximal isometric contraction in two muscles acting upon the same joint but differing in muscle fibre composition. Surface and intra‐muscular EMG activity from the gastrocnemius and soleus muscles and IFT were recorded during an exhausting isometric plantar flexion (30% of maximal voluntary contraction). Surface EMG amplitude (RMS) of both gastrocnemius and soleus muscles increased significantly over time. Gastrocnemius EMG RMS increased in a non‐linear fashion while soleus EMG RMS increased linearly. A significant linear decrease of surface EMG mean power frequency (MPF) was observed over time for both muscles. The decrease in gastrocnemius MPF was significantly greater than that for soleus. Intra‐muscular EMG results showed similar trends. Correlations of intramuscular EMG RMS and MPF with time were, however, characterized by lower correlation coefficients than those from the surface EMG. Isometric force tremor RMS significantly increased non‐linearly with duration of contraction, while IFT MPF showed a significant linear decrease with time. Changes in surface EMG RMS were correlated to changes seen in IFT RMS, in particular, for the predominantly fast twitch gastrocnemius muscle. Correlation coefficients of surface EMG MPF and IFT MPF were lower than RMS correlations. The associated changes in IFT and EMG with fatigue indicate alterations in motor unit firing rate, recruitment and synchronization. The muscle specificity of the EMG and IFT changes suggests a coupling to muscle fibre type composition, although differences in the relative force contribution of each muscle could also affect th

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1994.tb09786.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

We investigated the mechanism(s) by which angiotensin converting enzyme (ACE)‐inhibition and angiotensin (Ang) II influence peripheral sympathetic neurotransmission in canine gracilis musclein situ, with a‐adrenoceptors either intact or irreversibly blocked by phenoxybenzamine. ACE‐inhibition by ramiprilat reduced, and subsequent infusion of Ang II (30 ng kg‐1min‐1i.v.) markedly increased arterial plasma Ang‐(1–8)octapeptide levels, basal muscle perfusion pressures and mean arterial pressure. Local intra‐arterial bolus injection of Ang II caused marked vasoconstriction followed by vasodilation. This vasoconstrictor response was enhanced and the ensuing vasodilation was abolished following prostaglandin synthesis inhibition by diclofenac. The vasoconstrictor response to low frequency (0.5 Hz) sympathetic nerve stimulation was also enhanced by diclofenac. The nerve stimulation‐evoked noradrenaline (NA) overflow was reduced by ramiprilat when a‐adrenoceptors were blocked (‐ 11 ± 3 %,P<0.05), but increased when a‐adrenoceptors were intact (+ 28± 14%,P<0.05). During ACE‐inhibition, effective bradykinin receptor antagonism by HOE 140 reduced stimulation‐evoked NA overflow irrespective of a‐adrenoceptor blockade (i.e. by 25 ± 5 and 20 ± 3% in the absence and presence of a‐adrenoceptor blockade, respectively,p<0.01). Diclofenac increased stimulation‐evoked NA overflow in the absence of a‐adrenoceptor blockade (+ 19 ± 4%,P<0.05). I.v. infusion of Ang II failed to enhance stimulation‐evoked NA overflow both before and after diclofenac.In conclusion, the results support the ideas that local formation of Ang II and bradykinin facilitate, and of prostaglandins inhibit NA release, and that ACE inhibition influences sympathetic neurotransmission through all of these mechanisms in skeletal musclein situ;the net result depends on the degree of prejunctional a‐adrenergic feedback inhibition. Circulating Ang II may enhance the local formation of vasodilatory prostaglandins, but does not seem to modulate NA release even after prostaglandin synthesis inhibition in this model. Our data suggest that circulating Ang II may not reach the perivascular sympathetic nerves to a

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1994.tb09787.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The aim of the present study was to analyse quantitatively, on a cat gastrocnemius preparationin vivo, the effects of i.a. or i.v. administered glyceryl trinitrate (GTN), sodium nitroprusside (SNP) or nitric oxide (NO dissolved in saline) on vascular resistance (tone) in the following consecutive vascular sections: Large‐bore arterial resistance vessels (>25 μm), small arterioles (<25 μm), and the veins. Effects on hydrostatic capillary pressure(Pcv) and transcapillary fluid exchange were simultaneously recorded. Close‐arterially infused GTN (1–4096μg kg tissue‐1min‐1), SNP (0.5–32 %mUg kg tissue‐1min‐1) and NO (0.14‐0.82 mg kg tissue‐1min‐1) elicited a generalized dose‐dependent dilator response in all three sections, though with a preferential action on the arterial side. Further, these agents caused an increase inPcvand transcapillary fluid filtration. The sites of action along the vascular bed of these exogenous vasodilators differed from that previously established for endogenous EDNO. Infusion of GTN, SNP and NO during EDNO blockade (L‐NAME) could, therefore, not restore the vascular resistance distribution to that prevailing in the initial control state. Myogenic vascular reactivity to standardized transmural pressure stimuli was clearly depressed by GTN and SNP. Intravenously infused GTN (4–512 μg kg body wt‐1min‐1) and SNP (4–64μg kg body wt‐1min‐1) decreased arterial pressure and elicited, via reflex sympathetic activation, a dose‐dependent vasoconstriction in skeletal muscle, a decrease inPcv, and net transcapillary fluid absorption. The constrictor response thus overruled the direct dilator effect of the drugs. The plasma volume expansion known to result from long‐term systematic administration of nitrovasodilators seems in part to be caused by tran

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1994.tb09788.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY