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Biomedical subjects

K Kitani

Publications and source records attributed to K Kitani.

At least 145 records · Page 8Linked to original sources

Effects of cisapride on the pancreatic exocrine secretion in rats.

Exocrine pancreatic secretion to intravenous injections of a new stimulant of gastrointestinal motility, R51,619 (cisapride) was studied in conscious rats, and in the isolated pancreatic acini in vitro. The injection of cisapride (2 mg/kg) significantly increased fluid, bicarbonate and protein output in vivo. Atropine completely abolished the pancreatic responses to cisapride, and CR 1409, a new glutaramic acid derivative and a competitive cholecystokinin (CCK) inhibitor, tended to decrease the cisapride-induced pancreatic exocrine secretion. However, amylase release and Ca2+ efflux from the isolated pancreatic acini were not stimulated. These results suggest that cisapride indirectly affects the pancreatic exocrine secretion primarily by releasing acethycholine from the intrapancreatic nerve endings and in part by releasing CCK from the duodenum, but has no direct action on the pancreas.

Acetylcholine↗

Effect of somatostatin on pancreatic enzyme secretion.

The effect of somatostatin (SS) on the pancreatic enzyme secretion was studied in a perfusion system using dispersed pancreatic rat acini in vitro. In addition the effect of SS on pancreatic secretion in vivo was also studied in conscious rats for comparison. In an in vitro study, 6 x 10(-7) M SS-14 caused no significant change in amylase release when added 20 min before stimulation by 10(-5) M carbamylcholine (Cch), 10(-6) M A23187, 5 x 10(-7) M secretin and 2 mM dibutyryl cyclic AMP. The addition of 6 x 10(-7) M SS-28 also caused no significant change in amylase release stimulated by 10(-5) M Cch. High performance liquid chromatographic examination indicated that no degradation of either SS-14 or SS-28 occurred after reaction with dispersed acini. In an in vivo study SS-14 caused marked inhibition of basal pancreatic secretion and stimulated pancreatic secretion by bile-pancreatic juice diversion. These results indicate that SS has no direct inhibitory action on rat pancreatic secretion, and that SS may inhibit the pancreatic secretion by indirect mechanisms.

Amylases↗

Age-dependent decrease in the lethal threshold of pentylenetetrazole in mice.

We previously reported that the minimal effective concentrations in plasma and brain for inducing the maximal seizure after intraperitoneal injection of pentylenetetrazole (PTZ) significantly increased with age in mice. We also observed that some old mice died without the maximal seizure during the observation period of 15 min. To examine how the lethal dose changes with age in the mouse, in the present study we employed a continuous intravenous infusion of PTZ that enabled us to control the dose, either stopping the infusion after the maximal seizure or continuing it until the lethal dose was reached. This study has demonstrated that the lethal threshold of PTZ in the oldest mice (27 months for males and 30 months for females) was significantly lower than that for the respective younger groups. We conclude that our observation in old mice of death occurring before the appearance of maximal seizure is due to a decrease in the lethal threshold combined with an increase in the threshold for maximal seizure.

Aging↗

Possibilities and limitations of the smearing technique for cellular studies in compact tissues: a transmission electron microscopic analysis of liver smears.

During the last decade a sophisticated biophysical technique called fluorescence recovery after photobleaching (FRAP) has become available for the measurement of lateral diffusion constants of lipids and proteins in the cell membrane. The information obtainable by this method is of great importance; however, the applicability of this method is seriously hindered by the fact that it has been elaborated mostly for isolated, individual cells. On the other hand, the use of freshly prepared cells from compact tissues for such studies is highly desirable. Therefore, a special smearing method was devised (using liver cells) for this purpose. The present paper describes (i) the method of standardization of the smearing technique, (ii) the ultrastructural features of the liver cells when studying the liver smears by means of transmission electron microscopy. The possibilities and limitations of this method are discussed. According to the observations, under well-defined conditions the structural integrity of hepatocytes is maintained in the liver smears to such an extent that they are suitable for FRAP experiments.

Animals↗

The neurotoxicity of phenobarbital and its effect in preventing pentylenetetrazole-induced maximal seizure in aging mice.

The effects of age on the neurotoxicity of phenobarbital and its anticonvulsant effect were examined in female BDF1 mice of different ages by means of a rotorod test and the pentylenetetrazole (PTZ)-induced maximal seizure, respectively. The minimal neurotoxic concentrations (MTCs) of phenobarbital in both plasma and brain evaluated by a rotorod test were 50% lower (p less than 0.05) in old (24-months-old) mice compared with the respective values in young (6-months-old) mice, while 12-months values were the highest of the three groups. Mice given some dosages of phenobarbital, particularly old (24-months-old) mice, died within the 15-min observation period after an i.p. injection of PTZ (150 mg/kg) without demonstrating a hindlimb extensor component (HLE) of maximal seizure. When these animals were classified as responders with regard to the anticonvulsant effect of phenobarbital, the minimal effective concentrations (MECs) in plasma and brain required for abolishing the PTZ-induced maximal seizure in old mice were only 10-20% those of young mice. Present results coupled with our past studies using electroshock seizure suggest that both the neurotoxicity and the efficacy of phenobarbital increase with age in mice.

Administration, Oral↗

The age-dependent decline in the biliary transport maximum of conjugated sulfobromophthalein in the rat.

In order to elucidate the effect of aging on the biliary transport of organic anions, we examined the biliary transport maximum (Tm) for sulfobromophthalein (BSP) conjugated with glutathione in male and female Fischer-344 rats of various ages (3, 6, 24 and 30 months) during the constant intravenous infusion of conjugated BSP. For young rats the Tm values for conjugated BSP were higher in females than in males in contrast to the reported higher Tm value in males infused with free (unconjugated) BSP. In both sexes, Tm values progressively decreased with age up to 30 months. The results suggest that the previously reported higher Tm value for young male rats compared to young females during free BSP infusion is due to the lower conjugation capacity in females, and that the biliary transport process per se is more efficient in females at least for organic anions like conjugated BSP. Furthermore, the results support the previously proposed hypothesis that the biliary transport mechanism per se is steadily affected by aging in rats of both sexes.

Aging↗

Neurohumoral control of liver functions during aging.

A profound influence of steroidal (and possibly growth) hormone change during aging on the P-450 functions has been found in male rats. Direct and rapid autonomic nervous controls on glycogen metabolism in the liver is also greatly affected by aging. However, neither the responses of isolated rat hepatocyte preparations to adrenergic agonists nor the bindings of hepatocyte surface membrane preparations to adrenergic ligands was found to change with age, suggesting that the age effect on autonomic nervous control may be of central (presumably hypothalamic) origin. The present methodology of evaluating the receptor functions using Scatchard plot analysis does not seem sufficient to explore the functional alterations of receptor systems during aging and a need for new approaches that can determine certain physicochemical alterations of receptor, namely the measurement of the lateral mobility of membrane proteins during aging, is proposed.

Aging↗

Effects of human pancreatic polypeptide on exocrine pancreatic function in conscious rats.

The effect of newly synthesized human pancreatic polypeptide (hPP) on pancreatic secretion stimulated by a diversion of bile-pancreatic juice (BPJ) from the intestine, and plasma hPP concentration were examined in conscious rats. Exogenous hPP infusion (1, 10 micrograms/kg/hr) inhibited pancreatic protein, bicarbonate and fluid outputs during BPJ diversion in a dose-dependent manner. During 1 and 10 micrograms/kg/hr hPP infusion plasma hPP immunoreactivity increased to 369 +/- 22.9 and 1,125 +/- 90.2 pg/ml, respectively. These results suggest that newly synthesized hPP has an inhibitory activity on exocrine function of the pancreas.

Animals↗

Inhibitory effect of CR-1409, a competitive inhibitor of cholecystokinin, on pancreatic exocrine secretion in the conscious rat.

The inhibitory effect of CR-1409, a new glutaramic acid derivative and a competitive inhibitor for cholecystokinin (CCK), on the basal and CCK-stimulated pancreatic secretion was examined in the conscious rat in vivo. Rats were prepared with cannulae draining pure bile and pancreatic juice separately and with a duodenal cannula and right and left jugular vein cannulae. Plasma CCK level increased to 3.65 +/- 0.79 and 19.9 +/- 4.47 pM (mean +/- S.E.) by a 2-hr infusion of 100 and 300 pmole/kg/hr of CCK-octapeptide (CCK-8), respectively. Simultaneous infusion of 170 nmole/kg/hr of CR-1409 completely abolished pancreatic responses to 100 pmole/kg/hr of CCK-8. Infusion of CR-1409 at rate of 57 nmole/kg/hr slightly but significantly inhibited CCK-8 (100 pmole/kg/hr)-stimulated secretion. Pancreatic responses to 300 pmole/kg/hr of CCK-8 were partially inhibited but not completely abolished by the 170 nmole/kg/hr of CR-1409. Neither the basal pancreatic secretion nor the bile secretion was affected by CR-1409. We conclude that CR-1409 inhibited CCK-stimulated pancreatic secretion in vivo.

Animals↗

Plasma basal concentration of pancreatic polypeptide (PP) does not increase with ageing in the female Fischer (F-344) conscious rat.

Plasma concentrations of pancreatic polypeptide (PP) were compared for young (6 to 12 month-old) and old (24 to 25 month-old) conscious female Fischer rats by means of a radioimmunoassay. Basal plasma PP concentration was not different between young and old rats, nor was PP release stimulated by cerulein in either age group. The mechanism of PP release in rats is quite different from that in other species such as dogs and humans.

Aging↗

The effect of oleate on pancreatic and bile secretion in the conscious rat.

The effects of sodium oleate infused into either the duodenum or the terminal ileum on bile and pancreatic secretion were examined in the conscious rat. Rats were prepared with cannulae draining pure bile and pancreatic juice separately, and with an ileal and two duodenal cannulae. A 40 mM taurocholate solution containing 7 mg/ml bovine trypsin was infused into the duodenum throughout the experiment to replace diverted bile-pancreatic juice to maintain the normal regulation of pancreatic secretion. The intraduodenal infusion of sodium oleate significantly increased pancreatic juice flow, protein, and bicarbonate outputs, whereas it did not affect bile secretion. Intravenous infusion of proglumide (300 mg/kg/hr) did not inhibit pancreatic secretion stimulated by intraduodenal infusion of sodium oleate. An intravenous infusion of atropine (100 micrograms/kg/hr) attenuated protein and fluid secretions but not that of bicarbonate in response to intraduodenal oleate. In contrast, the intraileal infusion of oleate had no effect on pancreatic secretion, whereas it decreased bile flow, bicarbonate, and bile salt outputs. In conclusion, sodium oleate introduced in the duodenum stimulates pancreatic secretion but oleate in the terminal ileum inhibits bile secretion.

Animals↗

Enhancing effect of bucolome on biliary excretion of ouabain and digoxin in the rat.

The effect of bucolome (1-cyclohexyl-5-n-butyl-2,4,6-trioxoperhydropyrimidine) on the biliary excretion of intravenously administered ouabain and digoxin was examined in rats. The intravenously administered [3H] ouabain (0.1 mg/100 g b wt) was more rapidly excreted in the bile in female rats than in males. Intraperitoneal administration of bucolome induced a two fold increase in bile flow rate, accompanied by a significant increase in biliary recovery of ouabain during first 10 min (by 100% in males and 50% in females) resulting in significantly higher 60-min total biliary recoveries in both sexes. In female rats 80% of radioactivity was recovered in the bile as an unmetabolized form after 10 min of intravenous administration of [3H] digoxin. Biliary excretion of the parent drug, digoxin, was also enhanced by intraperitoneal administration of bucolome. Although the underlying mechanism(s) remains unknown, it was shown that biliary excretion of both ouabain and digoxin was enhanced by bucolome, as was previously shown for ouabain in male rats.

Animals↗

Increasing anticonvulsant effect of AD-810 (zonisamide) in aging BDF1 mice.

The anticonvulsant efficacy of a newly developed anticonvulsant, AD-810 (zonisamide, 3-sulfamoylmethyl-1,2-benzisoxazole) was examined in relation to mouse age in three different age groups of female BDF1 mice (7-, 25- and 29-month-old). The minimal effective concentration (MEC) of AD-810 in both plasma and brain for abolishing the electroshock-induced maximal seizure steadily decreased with age, the 25- and 29-month values being 50 and 30% of respective 7-month values. The observation in the present study was almost identical to previous observations by the authors on phenytoin, phenobarbital and oxazepam. The present results support our previous contention that the dose and plasma concentration of anticonvulsants can (and probably should) be reduced in the elderly regardless of the drug. Since the anticonvulsant mechanism of AD-810 has been reported to differ from those of previously examined drugs (phenobarbital and oxazepam), the results also suggest that the apparent increase in the pharmacological effect of these anticonvulsants may be due to old animals' lowered response capability for seizures rather than a specific age effect on the pharmacological reaction sites for individual anticonvulsants.

Aging↗

The mobility of concanavalin A receptors and surface immunoglobulins on rat hepatocyte plasma membranes.

Lateral mobilities of lectin receptors and surface immunoglobulins were measured in plasma membranes of hepatocytes prepared by smearing small pieces of rat liver tissue and then using the fluorescence recovery after photobleaching (FRAP) technique. Smears were treated with various doses of fluorescein isothiocyanate (FITC) conjugated concanavalin A (ConA), succinylated ConA (SConA), wheat germ agglutinin (WGA), and soybean agglutinin (SBA), as well as with rabbit anti-rat IgG (RARa/IgG) and goat anti-rat IgM(Fc) (GARa/IgM(Fc] antisera. 10 micrograms/ml ConA and SConA concentrations and a 55 X dilution of the GARa/IgM(Fc) antiserum were found to be suitable for measuring the lateral mobilities dependent on age. Diffusion constant and mobile fractions of receptor complexes were measured in different age groups of female Fisher rats (from 1 to 26 month-old). The FRAP measurements revealed that at least two major receptor sites can be distinguished in cell membranes of compact tissue (similar to the cultured and isolated cells), forming a mobile and an immobile fraction. The mobile fractions of both the lectin receptors and the surface immunoglobulins tended to decrease with age, while the age differences of the diffusion constants were not statistically significant. The observed alterations could be due to the covalent crosslinking of the mobile receptors to immobile patches and/or to the retardation of free diffusion by the cytoskeleton, dependent on age.

Aging↗