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PubMed2003

Bile secretory function after warm hepatic ischemia-reperfusion injury in the rat.

Hepatic ischemia-reperfusion (I-R) injury frequently is associated with cholestasis. However, the underlying mechanisms are not fully understood. The aim of the study is to assess bile secretory function in vivo in rats subjected to warm lobar hepatic ischemia at different times during reperfusion. A model of lobar 70% warm hepatic ischemia for 30 minutes was used with studies conducted at 1 and 6 hours and 1, 3, and 7 days after reperfusion. Bile secretory function was assessed after selective cannulation of bile ducts of ischemic (ILs) and nonischemic lobes (NILs). Serum activity of hepatic alanine and aspartate aminotransferase was slightly increased in rats subjected to I-R, whereas serum bile salt levels increased early during reperfusion, returning to control values after 7 days. ILs showed mild reversible leukocyte infiltration and no significant necrosis. Bile flow and bile salt excretion were significantly decreased in ILs during the first 24-hour reperfusion period compared with sham-operated rats and NILs. A marked reduction in glutathione (GSH) excretion occurred at 1 and 6 hours and 1 and 3 days, which returned to control values after 7 days. Total GSH and both reduced and oxidized GSH levels in liver homogenate and arterial blood GSH levels were unchanged at all times. Protein mass of multidrug resistance protein 2 and its function, assessed by the hepatic maximum secretory rate of ceftriaxone, did not show significant changes in ILs or NILs compared with sham-operated rats. Liver tissue gamma-glutamyl transpeptidase (GGT) and gamma-glutamylcysteine synthetase activities remained unchanged, whereas biliary GGT and cysteine secretory rates were significantly increased in ILs and NILs. Administration of acivicin, a GGT inhibitor, resulted in decreased secretion of this enzyme into bile and a parallel marked increase in biliary GSH secretion compared with untreated ischemic rats. In conclusion, warm hepatic I-R induces reversible cholestatic changes in ILs. GSH secretory rates from both ILs and NILs were markedly decreased during reperfusion. The reversibility of this effect after GGT inhibition, as well as increased release of active GGT into bile and cysteine biliary secretory rates, suggest increased GSH degradation in bile. These findings might be relevant for the I-R-induced clinical cholestasis, as well as cholangiocyte injury, seen after hepatic ischemia.

Animals↗
PubMed1976

A comparative study of adrenal progesterone secretion during the estrous cycles of hamsters and rats.

Adrenal secretory rates and peripheral plasma levels of progesterone (PROG) were determined during the estrous cycles of hamsters and 4-day cyclic rats. In both species, the PROG concentrations in peripheral plasma were never more than 6% of those observed in adrenal venous plasma. In hamsters, adrenal PROG secretory rates varied from 3.8 +/- 0.8 ng/min at 0800 hr on proestrus (P) to 8.5 +/- 1 ng/min at 2000 hr on estrus (E). The rates noted on P were among the lowest observed and were similar to those noted at 0800 hr the following morning. In rats, adrenal PROG secretory rates varied from 57 +/- 9 ng/min at 0800 hr on E to 130 +/- 18 ng/min at 2000 hr on P. A significant decline occurred between 2000 hr on P and 0800 hr the following morning. Rats secreted 3 to 8 times more PROG than did hamsters when the secretory rates are expressed as ng/min/100 mg adrenal. In hamsters, the data suggest a relative lack of influence of female reproductive hormones on adrenal PROG secretion and in turn the latter may not be involved in reproductive hormonal changes leading to ovulation. In rats, the increased adrenal PROG secretion noted on P may be due to the influence of reproductive hormones on adrenocortical function. This elevated rate may in turn influence the hypothalamo-hypophyseal-ovarian axis.

Adrenal Glands↗
PubMed1983

Taurocholate, but not taurodehydrocholate, increases biliary permeability to sucrose.

To determine whether bile salts alter the permeability of the biliary tree to inert solutes, we investigated the effects of taurocholate and taurodehydrocholate on [14C]sucrose bile-to-plasma ratio in the situ perfused rat liver. Sucrose bile-to-plasma ratio remained virtually constant over a 3-h period in untreated rats. Infusing increasing amounts of taurocholate produced the anticipated dose-dependent increase in bile flow and bile salt secretion up to a maximal secretory rate of 278 nmol X min-1 X g liver-1. When the secretory rate was exceeded, bile flow decreased by 22%. Even at doses below the maximal secretory rate, sucrose bile-to-plasma ratio increased in a dose-dependent fashion. To determine whether this was due to recruitment of more permeable centrizonal hepatocytes, the effect of equimolar amounts of taurodehydrocholate was determined. This nonmicelle-forming bile salt led to more marked choleresis than taurocholate but did not affect sucrose bile-to-plasma ratio. We conclude that taurocholate, but not taurodehydrocholate, leads to a dose-dependent increase in biliary permeability.

Animals↗
PubMed1992

Effect of dietary sodium on atrial natriuretic factor released in rats with chronic renal failure.

Studies were done in partially nephrectomized rats to examine the effect of dietary sodium intake on atrial natriuretic factor (ANF) released by the atria. Experiments were done in four groups of male Wistar rats. Group 1 (n = 10) and 3 (m = 10) rats were sham-operated. Group 2 and 4 were 5/6 nephrectomized. Group 1 and 2 were fed a sodium-supplemented diet. Group 3 and 4 received a sodium-deficient diet. Renal functions were similar between group 2 and 4. Plasma ANF level was raised in group 2 (182 +/- 17 pg/ml). Circulating ANF levels in group 1,3 and 4 were 95 +/- 5, 90 +/- 5 and 95 +/- 4 pg/ml, respectively. Atrial ANF contents were higher in partially nephrectomized rats after receiving a sodium-supplemented diet. A reduction in atrial ANF contents occurred when fed a sodium-deficient diet. In vitro studies were done to assess the rate of ANF released. ANF secretory rates were highest in group 2 (11 +/- 1.5 pg/min/mg). There was no difference between group 1,3 and 4. A positive correlation was found between plasma ANF and ANF released in all groups examined. Thus, plasma ANF levels were a good reflection of ANF secretory rates. A significant correlation existed between plasma ANF and sodium excretion in chronic renal failure rats (r = 0.78; p less than 0.01). A dissociation between plasma ANF and water excretion was seen. These results suggest that in chronic renal failure rats, ANF played a role in sodium adaptation.

Adaptation, Physiological↗
PubMed1983

Effect of fatty acids on lipid and apoprotein secretion and association in hepatocyte cultures.

Increasing availability of free fatty acids (FFA) to liver results in enhanced rates of secretion of triglycerides in lipoproteins. However, as FFA uptake increases, triglyceride secretory rates reach a plateau and esterified fatty acids accumulate intracellularly, suggesting that something is limiting lipid transport out of the liver. One possibility could be the limited availability of apoproteins. To test this hypothesis, primary rat hepatocytes in culture were incubated with increasing amounts of FFA (0-2.1 mumol/dish) and the amounts of lipids and apoproteins inside the cells and in culture media were measured; the latter by specific radioimmunoassays. Media also were fractionated on Sepharose 2B and 6B columns and the elution profiles of apoproteins were obtained. With exposure to increasing amounts of free fatty acids, hepatocytes took up more fatty acids and intracellular levels of triglycerides rose (from 71 to 146 micrograms/mg cell protein). Concomitantly, media triglycerides nearly doubled (31 to 51 micrograms/mg). Incorporation of [3H]glyceride into cellular and media triglyceride also rose. However, levels of apoproteins A-I, B, C-III3, and E in cells and media were unchanged. The increasing amounts of triglycerides in media were present in larger particles, as demonstrated on gel permeation chromatography. The elution profiles of apoproteins B, C-III3, and E were altered in that a greater proportion of the apoproteins eluted with larger particles. Similar results were obtained when hepatocytes were preloaded with increasing amounts of FFA over 12 h and analyses of cells and media were carried out 8 and 22 h after removal of fatty acids from the media. During loading of cells, accumulation of cellular triglycerides was directly related to media FFA concentrations. During unloading, triglyceride secretory rates were related to cellular triglyceride levels. At higher triglyceride secretory rates larger particles were secreted and a greater proportion of apoproteins was associated with the larger particles, but total amounts of apoproteins in the system did not change. These data lead us to suggest that enhanced rates of apoprotein synthesis need not occur in the response to acute changes in hepatic lipid transport, rather, increased secretion of lipid is brought about by augmented intracellular lipid apoprotein association.

Animals↗
PubMed1995

Increased disorderliness and amplified basal and pulsatile aldosterone secretion in patients with primary aldosteronism.

To investigate the pathophysiology of altered aldosterone secretion in patients with primary aldosteronism, the pulsatile mode of in vivo aldosterone and cortisol release was examined by quantitative deconvolution analysis in 5 normal subjects (controls) and 10 patients with aldosterone-producing adenomas (APA) under conditions of sodium (150 meq/day) balance. Episodic release of aldosterone and cortisol was assessed by sampling blood at 10-min intervals for 24 h. A waveform-independent deconvolution algorithm was used to calculate endogenous aldosterone and cortisol secretion rates on a sample by sample basis in each subject. There were no differences in the number of aldosterone or cortisol secretory bursts per day or their mean interpulse intervals between normal subjects and patients with primary aldosteronism. A 24-h rhythmicity in serum aldosterone concentrations was maintained in APA patients. Patients with primary aldosteronism had significantly higher (P < 0.01) aldosterone mean secretory rates, mean mass of aldosterone secreted per burst, maximal aldosterone secretion rates attained within each burst, and mean basal (nadir) aldosterone secretion rates. A recently introduced regularity statistic, approximate entropy (ApEn), was used to test for orderliness (small ApEn) vs. randomness (large ApEn) in the aldosterone time series. ApEn was significantly larger for the APA patients (1.433 +/- 0.148) than for normal subjects (0.306 +/- 0.098; P < 0.001), with complete group segmentation yielding 100% sensitivity and specificity. In contrast, a scale-invariant form of this measure, normalized ApEn, showed no significant distinction between tumoral and normal aldosterone release patterns. These ApEn findings taken together are consistent with the deconvolution results from an entirely distinct perspective, reinforcing an amplitude difference, but no frequency difference, between normal subjects and APA patients. Unexpectedly, patients with APA had significantly lower mean cortisol secretory rates, reduced cortisol secretory burst mass, and attenuated maximal cortisol secretory rates than normal subjects (P < 0.01). Plasma cortisol and aldosterone concentrations in patients remained positively correlated over short time lags. In summary, the present findings demonstrate that in normal subjects and patients with APA, both aldosterone and cortisol are secreted in a burst-like mode. The presence of substantial basal aldosterone release and increased irregularity of serial aldosterone concentrations distinguishes APA from normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Long term culture of primary rat pituitary adrenocorticotropin/endorphin-producing cells in serum-free medium.

Insulin, transferrin, and serum albumin were found to be essential additives for maintenance of primary rat pituitary ACTH/endorphin cells in complete serum-free defined medium (CSFM). Primary anterior pituitary cultures maintained in CSFM exhibited a 3- to 5-fold increase in cell content of ACTH/endorphin-related peptide during the first 2 weeks in culture, and this level remained stable for at least the next week. Immunocytochemical and morphometric studies indicated that the number of corticotropes increased only slightly, so that hormone content per corticotrope increased. Anterior pituitary cultures maintained in CSFM exhibited a basal secretory rate of 0.3-0.4% of cell hormone content/h throughout the 3-week period in culture, and total hormone production increased 6-fold. Primary anterior pituitary cultures maintained chronically in CSFM containing 10 nM CRF demonstrated a 15- to 20-fold increase in total ACTH/endorphin production over 3 weeks in culture. Chronic treatment with CRF brought about a sustained 6-fold increase in secretory rate (2.5% of cell hormone content/h), and corticotrope content of hormone was diminished 3-fold. Corticotropes maintained chronically in CSFM containing CRF did not increase in number and exhibited a rim of immunocytochemically identifiable hormone around the cell periphery. Anterior pituitary cultures maintained chronically in CSFM containing 100 nM dexamethasone (DEX) exhibited decreased cell hormone content and an unaltered secretory rate. In the DEX-treated cultures the number of immunocytochemically identifiable corticotropes declined, as did the staining intensity per corticotrope. Primary cultures of rat intermediate pituitary cells maintained in CSFM exhibited a 1.5- to 2-fold increase in hormone content after 1-2 weeks in culture, maintained a constant basal secretory rate of 0.4-0.5% cell content/h, and were not responsive to chronic treatment with CRF or DEX.

Adrenocorticotropic Hormone↗
PubMed1982

Heterogeneity of organic base secretion by proximal tubules.

Rabbit renal tubules were perfused in vitro to characterize the secretion of the organic base procainamide by proximal tubules. When [3H]-procainamide was added to the bath it was secreted into the tubule lumen. In tubules from superficial nephrons secretory rates were greatest in S1, intermediate in S2, and lowest in S3 segments. In juxtamedullary tubules secretory rates were greatest in S1 and S2 and lowest in S3 segments. Secretory rates of p-aminohippurate were greatest in S2 and lowest in S1 and S3 segments of both superficial and juxtamedullary nephrons. The results indicate that there is both axial and internephronal heterogeneity for the secretion of this organic base by rabbit proximal tubules. The segmental secretion of procainamide differs from that of p-aminohippurate.

Aminohippuric Acids↗
PubMed1991

Adaptive regulation of hepatic bile salt transport: effects of alloxan diabetes in the rat.

The hepatic transport of bile salts appears to be adaptively regulated by changes in the bile salt pool size and in the flux of bile salt through the liver. The maximum secretory rate of taurocholate increases or decreases when the bile salt pool size is modified by either oral feeding of cholate or taurocholate (up-regulation) or prolonged bile salt depletion through a biliary fistula (down-regulation), respectively. It is not known whether adaptive regulation of hepatic bile salt transport operates under conditions in which the bile salt pool size is modified by endogenous changes in bile acid metabolism. Because experimental diabetes mellitus is associated with alterations in the synthesis of bile acids and total bile salt pool size and composition in the rat, we examined the effects of diabetes mellitus induced by alloxan (5 mg/100 gm body weight, intravenously) and insulin treatment on hepatic bile salt transport and relate the changes to bile salt pool size variations. At 3 days after alloxan injection (DIAB-3 group) both taurocholate maximum secretory rate and pool size were significantly decreased, whereas they were restored to normal values after 6 days of diabetes (DIAB-6 group). Insulinopenic diabetes for 14 days (DIAB-14 group) and for 24 days (DIAB-24 group) resulted in a marked increase of basal bile salt secretory rate (secondary to an increased contribution of cholate conjugates) and an enhanced taurocholate maximum secretory rate compared with control rats (147% and 188% increase, respectively) and with a group (PHARM-control) that received alloxan but did not develop detectable glycosuria (224% and 286% increase, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1969

Metabolism and rate of secretion of aldosterone in the bullfrog.

A study of the metabolism of aldosterone in the bullfrog was undertaken to provide a measurable metabolite for the indirect isotope dilution technique for measuring secretory rates. The rate of excretion of labeled aldosterone was considerably slower in the frog than in man and made necessary the collection of excretory products for 5 days to insure reasonably complete recovery of metabolites. The major identifiable metabolite was a tetrahydro derivative subsequently identified as 3beta-hydroxy-5beta-tetrahydroaldosterone. This metabolite was excreted partly in the free form and partly as a glucuronic acid conjugate. The pH 1-hydrolyzable conjugate of aldosterone was not detected. For the measurement of secretory rates, aldosterone-(3)H was injected into the dorsal lymph space and the animal placed in a bath to provide an environment of constant electrolyte composition and intake and a means of collecting excretory products. Urine and bath fluid were collected for 5 days, tetrahydroaldosterone was isolated, and its specific activity determined for the calculation of the aldosterone secretory rate. The rate of secretion of aldosterone in the bullfrog was increased by a tap water bath and by bovine adrenocorticotropic hormone, decreased by a saline bath and by dexamethasone, and unchanged by valine-5-angiotensin amide.

Adrenocorticotropic Hormone↗
PubMed1991

Natriuretic peptides as cardiac hormones in normotensive and spontaneously hypertensive rats. The ventricle is a major site of synthesis and secretion of brain natriuretic peptide.

To study synthesis, storage, and secretion of brain natriuretic peptide (BNP) in the heart, we have measured BNP mRNA and BNP concentrations in the hearts of Wistar-Kyoto rats and also have investigated its secretion from the isolated perfused heart. The atrium expressed the BNP gene at a high level, and a considerable amount of BNP mRNA also was present in the ventricle, which corresponded to approximately 40% of the atrial BNP mRNA concentration. When tissue weight was taken into account, the total content of BNP mRNA in the ventricle was approximately threefold larger than that in the atrium, although the atrial natriuretic peptide (ANP) mRNA content in the ventricle was only 7% of that in the atrium. By contrast, the BNP concentration in the ventricle was 4.07 +/- 0.97 pmol/g, which was less than 1% of that in the atrium (451 +/- 86 pmol/g). The basal secretory rate of BNP from the isolated perfused whole heart was 49.3 +/- 6.1 fmol/min, approximately 60% of which was maintained even after atrial removal, whereas the secretory rate of ANP was reduced to less than 5%. We also studied age-matched spontaneously hypertensive rats-stroke prone. The rank order of the BNP mRNA concentration in the hearts of these rats was left ventricle greater than right ventricle greater than right atrium = left atrium, and the total BNP mRNA content and BNP secretory rate in the ventricle were twice as large as in Wistar-Kyoto rats. These results demonstrate that BNP is a novel cardiac hormone in rats and is predominantly synthesized in and secreted from the ventricle. This is in striking contrast to ANP, which occurs mainly in the atrium. The results also suggest possible pathophysiological roles of BNP in certain cardiovascular disorders.

Animals↗
PubMed1990

Effect of bismuth subcitrate and sucralfate on rat duodenal and human gastric bicarbonate secretion in vivo.

Acid and alkali secretion have been examined together with prostaglandin E2 production in response to two mucosal protective drugs, colloidal bismuth subcitrate and sucralfate. Doses of colloidal bismuth subcitrate in the therapeutic range (120 and 1200 mg) had no effect on alkali secretion or luminal PGE2 output when perfused into the stomach of human volunteers. Similarly, in the anaesthetised rat, neither gastric acid nor duodenal alkali secretions were influenced by iv (12 mg/kg) or topical (120 mg/ml) administration of colloidal bismuth subcitrate. In contrast, perfusion of the human stomach with 1 g sucralfate stimulated bicarbonate output by 50%, a response which was unaffected by indomethacin (25 mg/h). A rise of 64% in gastric PGE2 output after sucralfate was, however, prevented by indomethacin pretreatment. Alkali secretion by rat duodenum was also increased by sucralfate but the response depended on the basal secretory rate. Low basal secretors (less than 3 mumol) showed a 75% stimulation whereas rats with high basal secretory rates (greater than 3 mumol) showed no significant response. All duodenal preparations regardless of basal secretory rate showed a stimulation of bicarbonate output with topical PGE2. The results suggest that enhancement of gastroduodenal bicarbonate secretion may play a role in the protective action of sucralfate but is unlikely to explain mucosal protection by colloidal bismuth subcitrate.

Adolescent↗
PubMed1997

Osmotic flow transients during acetylcholine stimulation in the perfused rat submandibular gland.

Osmotic stress was applied to the perfused rat submandibular gland during steady-state fluid secretion. Alterations of perfusate osmolarity, by addition or withdrawal of sucrose or NaCl, caused transient changes in secretory rate during continuous stimulation with 1 microM acetylcholine (ACh). Hyposmotic perfusates transiently increased, and hyperosmotic perfusates transiently reduced, the secretory rate. The transients were attributed to changes in osmotic flow resulting from changes in the instantaneous transepithelial osmotic gradient. The time course of the change in interstitial osmolarity was determined by using a Cl- electrode to record the changes in interstitial Cl- concentration following a step change in perfusate Cl- concentration. From the calculated changes in interstitial osmolarity and the resulting changes in secretory rate, the osmotic water permeability of the secretory pathway was estimated to be greater than 15.0 +/- 1.2 microliter (mosmol 1-1)-1 min-1 (g wet weight)-1 (9.8 x 10(-6) +/- 0.8 x 10(-6) l atm-1s-1g-1). The transepithelial gradient required to sustain steady state, ACh-evoked secretion would therefore be less than 16 mosmol l-1 NaCl, which is consistent with previous micropuncture data indicating that the luminal fluid is approximately isosmotic.

Acetylcholine↗
PubMed1986

Altered phospholipid secretion in type II pneumocytes isolated from streptozotocin-diabetic rats.

To study the effect of diabetes on pulmonary surfactant secretion, type II pneumocytes from adult streptozotocin-induced diabetic rats were placed in short-term culture. As opposed to a linear secretory rate by control type II cells, the secretory rate of type II cells from diabetic animals was biphasic reaching a minimum at 1.5 h. When exogenous surfactant containing radioactive phosphatidylcholine was added to the incubation media for 1.5 h, the cells from diabetic animals incorporated more exogenous phosphatidylcholine into lamellar bodies than control cells. This suggests that in the type II cell from diabetic animals, the rate of reutilization is greater than the rate of secretion until 1.5 h, at which time the rate of secretion becomes greater. The altered secretory pattern was reversed by in vivo insulin treatment 30 min prior to killing but not by the addition of insulin to the incubation media. When challenged by isoproterenol, a beta-adrenergic agonist, the secretory pattern of cells from diabetic animals was biphasic as observed with basal secretion; however, secretion was stimulated 30% as opposed to 100% increase in control cells. These data suggest that basal and stimulated secretion are altered in the cultured type II cell from diabetic animals and restored by in vivo but not in vitro insulin treatment.

Animals↗
PubMed1980

Substrate dependency for HCl secretion by isolated piglet gastric mucosa.

Gastric mucosa was isolated from newborn piglets and bathed with balanced salt solutions. In the presence of glucose (ca. 0.01 M), this gastric preparation has been shown to be responsive to histamine by relatively prompt and vigorous H+ secretory rates. Secretion is dependent on glucose concentration in the serosal bathing solution, showing saturation kinetics with an apparent Km of about 2 mM glucose. Acetate and pyruvate were about as effective as glucose in sustaining H+ secretory rates. Short-chain fatty acids supported secretory rates that were significantly lower than rates measured with glucose. The order of effectiveness was butyrate greater than valerate greater than hexanoate greater than propionate. The results show absolute dependence of H+ secretion by piglet gastric mucosa on exogenous substrate and the preferential utilization of carbohydrate sources as substrates for secretion. They suggest that it is unlikely for any specialized and essential involvement of fatty acids in the primary H+ secretory mechanism as had been previously proposed.

Acetates↗
PubMed1991

Pancreatic secretion by the anaesthetized rabbit in response to secretin, cholecystokinin, and carbachol.

Considerable differences exist among species in the patterns of regulation of pancreatic secretion. Although rabbit pancreas is quite often used for in vivo and in vitro studies of pancreatic function, responses of this gland in vivo to common pancreatic stimuli have never been characterised in detail. That was the purpose of this study. The data demonstrate the existence of a spontaneous fluid secretion that can be increased by intravenous infusions of secretion (sevenfold), cholecystokinin-octapeptide (CCK8) (threefold), and carbachol (sixfold). The electrolyte composition of the secretion evoked by each of these stimuli was similar: sodium and potassium concentrations were constant and slightly higher than those in plasma at all secretory rates, whereas bicarbonate concentration rose with secretory rate to approach a plateau of about 125 mmol/L, and chloride concentration fell to a plateau of about 35 mmol/L. In terms of protein secretion, secretin caused a small but significant rise in output, while CCK8 and carbachol evoked the expected large increase. Thus, regulation of pancreatic electrolyte secretion in rabbit differs from that in dog, cat, and human, on the one hand, and rat, on the other hand, and most closely resembles the pattern observed in guinea pig.

Animals↗
PubMed1998

Cortisol secretion is related to electroencephalographic alertness in human subjects during daytime wakefulness.

To determine whether human hypothalamo-pituitary-adrenal axis activity is related to the alertness level during wakefulness, 10 healthy young men were studied under resting conditions in the daytime (0900-1800 h) after an 8-h nighttime sleep (2300-0700 h). A serial 70-sec gaze fixation task was required every 10 min throughout the daytime experimental session. The corresponding waking electroencephalographic (EEG) segments were submitted to quantitative spectral analysis, from which EEG beta activity (absolute power density in the 13-35 Hz frequency band), an index of central alertness, was computed. Blood was collected continuously through an indwelling venous catheter and sampled at 10-min intervals. Plasma cortisol concentrations were measured by RIA, and the corresponding secretory rates were determined by a deconvolution procedure. Analysis of individual profiles demonstrated a declining tendency for EEG beta activity and cortisol secretory rate, with an overall temporal relationship indicated by positive and significant cross-correlation coefficients between the two variables in all subjects (average r=0.565, P < 0.001). Changes in cortisol secretion lagged behind fluctuations in EEG beta activity, with an average delay of 10 min for all the subjects. On the average, 4.6+/-0.4 cortisol secretory pulses and 4.9+/-0.5 peaks in EEG beta activity were identified by a detection algorithm. A significant, although not systematic, association between the episodes in the two variables was found: 44% of the peaks in EEG beta activity (relative amplitude, near 125%; P < 0.001) occurred during an ascending phase of cortisol secretion, cortisol secretory rates increasing by 40% (P < 0.01) 10-min after peaks in EEG beta activity. However, no significant change in EEG beta activity was observed during the period from 50 min before to 50 min after pulses in cortisol secretion. In conclusion, the present study describes a temporal coupling between cortisol release and central alertness, as reflected in the waking EEG beta activity. These findings suggest the existence of connections between the mechanisms involved in the control of hypothalamo-pituitary-adrenal activity and the activation processes of the brain, which undergoes varying degrees of alertness throughout daytime wakefulness.

Adult↗
PubMed1990

Gabexate and camostat, synthetic proteinase inhibitors, as direct inducing factors of water and bicarbonate secretion in the isolated and blood-perfused dog pancreas.

The effects of proteinase inhibitors on the secretion of pancreatic juice were investigated in preparations of the isolated and blood-perfused dog pancreas as compared with those of secretin. Each drug tested was administered i.a. Graded doses of gabexate (1-10 mg) elicited dose-dependent biphasic responses for the secretory rates, bicarbonate concentrations and outputs of pancreatic juice, with maximum effects at approximately 5 mg, but had little effect on the protein concentrations. Camostat, at a high dose of 10 mg, caused significant increases in the secretory rate, bicarbonate concentration and output of pancreatic juice over their basal levels, but had little influence on the protein concentration. Secretin (0.03-0.3 U) usually produced similar to gabexate-induced results (1-5 mg). Both bicarbonate and protein concentrations of the juice obtained with gabexate or camostat were almost the same as those obtained with secretin at a similar secretory rate of pancreatic juice, suggesting the secretory action of gabexate or camostat might be similar to that of secretin. In addition, gabexate (3 mg) and camostat (10 mg) elicited more than the respective additive secretory responses in the presence of i.a. infusion of a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (12 micrograms/min) as well as secretin (0.1 U). These results indicate that gabexate and camostat induce water and bicarbonate secretion by acting directly on ductular cells of the dog pancreas, which might be mediated at least partially through cyclic AMP.

1-Methyl-3-isobutylxanthine↗