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Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men.

Mean plasma GH concentrations are controlled by the frequency, amplitude, and duration of underlying GH secretory bursts as well as by the half-life of endogenous GH. We investigated the specific mechanisms that subserve the clinically recognized negative effects of age and adiposity on mean serum GH concentrations. To this end, 21 healthy men, aged 21-71 yr, who were of nearly normal body weight underwent blood sampling at 10-min intervals for 24 h. Deconvolution analysis was used to estimate specific features of GH secretion and clearance. Compared to younger men, the older tertile of men had significant reductions in 1) GH secretory burst frequency, 2) the half-life of endogenous GH, and 3) the daily GH secretory rate, but not 4) GH secretory burst half-duration, amplitude, or mass. Linear regression analysis disclosed that age was a major negative statistical determinant of GH secretory burst frequency (r = -0.80; P = 0.005) and endogenous GH half-life (r = -0.70; P = 0.024). Body mass index, an indicator of relative obesity, was a significant negative correlate of GH half-life (P = 0.045) and GH secretory burst amplitude (P = 0.031). Age and body mass index each correlated negatively with the daily GH secretion rate (P = 0.0031 and P = 0.027, respectively), and together accounted for more than 60% of the variability in 24-h GH production rates (r = -0.78; P = 0.00056). On the average, for a normal body mass index, each decade of increasing age attenuated the GH production rate by 14% and the GH half-life by 6%. Conversely, each unit increase in body mass index, at a given age, reduced the daily GH secretion rate by 6%. We conclude that age and relative adiposity are distinct and specific correlates of individual attributes of GH secretion and clearance in men.

Adult↗

Effects of atrial natriuretic factor on urinary concentration of catecholamines and renin secretion in dogs.

This study evaluated the effects of synthetic atrial natriuretic factor (ANF) on renal hemodynamics, urinary excretion of electrolytes, norepinephrine (NE), and dopamine (DA); and renal production of renin in anesthetized dogs. Following a bolus (1 micrograms/kg body weight) and infusion (0.1 microgram/kg/min) for 30 min, there was significant increase in urine flow (220 +/- 41%), glomerular filtration rate (72 +/- 14%), and urinary sodium excretion (170 +/- 34%). There was a decrease in renin secretory rate and the concentration ratio of urine NE to DA following ANF was decreased (p less than 0.05). These data suggest that ANF decreases renal production of NE and renin.

Animals↗

Ethynylestradiol impairs bile salt uptake and Na-K pump function of rat hepatocytes.

Ethynylestradiol impairs bile flow and bile salt maximum secretory rate in rats, implying a secretory defect. In addition, Na-K-ATPase activity is decreased in liver surface membranes, suggesting abnormalities at the sinusoidal as well as the canalicular membrane. We investigated whether ethynylestradiol pretreatment affects bile salt uptake and Na-K pump function in isolated rat hepatocytes. Ethynylestradiol-treated cells were functionally intact as assayed with trypan blue exclusion, lactate dehydrogenase release, and oxygen consumption. Initial taurocholate uptake velocity was reduced by 73% in ethynylestradiol-treated hepatocytes [Vmax, 1.0 +/- 0.1 vs. 3.7 +/- 0.2 mumol X min-1 X (10(6) cells)-1; P less than 0.001; Km, 34 +/- 5 vs. 33 +/- 3 microM]. Na-K-ATPase activity in cell homogenates (36 +/- 5 vs. 27 +/- 4 mumol Pi X h-1 X mg prot-1; P less than 0.05), ouabain-suppressible rubidium-86 influx [6.8 +/- 1.1 vs. 4.8 +/- 1.0 nmol K+ X min-1 X (10(6) cells)-1; P less than 0.05], and intracellular potassium concentration (126 +/- 10 vs. 110 +/- 16 mmol/l; P less than 0.05) were reduced after ethynylestradiol. Taurocholate uptake measured at different temperatures between 25 degrees and 37 degrees was linear when plotted according to Arrhenius. The energy of activation was increased by 40% in ethynylestradiol-treated hepatocytes [17 +/- 4 vs. 23 +/- 4 kcal X mol-1 X (10(6) cells)-1; P less than 0.05], consistent with decreased membrane fluidity. These data suggest the possibility that during ethynylestradiol-induced cholestasis a disorder of the sinusoidal domain, caused perhaps by ethynylestradiol-induced alterations in membrane lipid composition, is an important contributing factor.

Animals↗

On the mechanism of renal vasoconstriction induced by acetylcholine in indomethacin-treated dogs.

Renal arterial infusion of acetylcholine (ACh) in control dogs produced a natriuresis and diuresis and an increase in renal plasma flow (RPF) without a change in glomerular filtration rate (GFR) or in renin secretory rate (RSR). In dogs pretreated with indomethacin (Indo), an inhibitor of prostaglandin synthetase, renal arterial infusion of ACh first produced a rise, then a decline in urine flow, sodium excretion (UNaV) and GFR that was accompanied by a progressive fall in RPF and a progressive rise in RSR. The rise in RSR was potentiated by renal arterial infusion of an alpha-adrenergic receptor blocker, phenoxybenzamine (Phenoxy), and attenuated, but not completely abolished, by beta-adrenergic receptor blockade with propranolol (Prop). Chemical denervation with reserpine alone, or in combination with chronic surgical renal denervation, failed to prevent the fall in RPF, GFR and UNaV and the rise in RSR produced by ACh in Indo-treated dogs. Renal arterial infusion of Phenoxy and intravenous infusion of Prop, alone or in combination with renal arterial infusion of an angiotensin II antagonist, saralasin, failed to maintain the vasodilatory, diuretic and natriuretic effects of ACh in Indo-treated dogs. Elimination of endogenous vasopressin by hypophysectomy also failed to prevent the vasoconstriction induced by ACh in Indo-treated dogs. The results suggest that ACh produced renal vasoconstriction in Indo-treated dogs by mechanism(s) other than an increase in renal adrenergetic activity or an increase in the activity of the renin-angiotensin system. The results also suggest that the vasoconstriction was independent of vasopresin.

Acetylcholine↗

A preliminary investigation of the effects of vasoactive intestinal peptide on secretion from the lingual salt glands of Crocodylus porosus.

Vasoactive intestinal peptide (VIP)-like immunoreactivity was demonstrated in the lingual salt glands of the estuarine crocodile, Crocodylus porosus. Varicose fibers showing VIP-like immunoreactivity ramified the salt glands, forming a dense network around the basal region of the exocrine cells. Secretions from the lingual salt glands were monitored in hatchling C. porosus. Spontaneous secretory activity was variable, ranging from 0.3 to 5.3 micromol Na 100 g(-0.7) bm hr(-1) (bm, body mass). Administration of a 100-microl bolus of 0.9% NaCl, via a cannulated femoral vein, did not affect the spontaneous secretory rate. However, injection of 100 pmol porcine VIP resulted in a massive increase in secretory activity, reaching a maximum of 58.2 micromol of Na 100 g(-0.7) bm hr(-1). The presence of VIP-like immunoreactivity and the positive secretory effect of administered VIP indicate a potential action of VIP on salt gland activity.

Alligators and Crocodiles↗

Effect of ethanol upon gastric emptying.

The effect of ethanol upon gastric emptying in healthy human subjects was studied by measuring the gastric emptying rates of three 750 ml meals, the osmolalities, energy densities, and pH of which were similar. Meal A, which contained 80 ml alcohol, emptied more rapidly than meal B, which contained 40 ml ethanol and 63.3 g dextrose; and meal B emptied more rapidly than meal C, which contained 126.6 g dextrose but no ethanol. The slower rate of emptying of the dextrose meal (C) was not due to an increased gastric secretory rate, as serial measurements of gastric pH were substantially and significantly higher with this than with the other two meals; nor was it due to a greater degree of duodenogastric reflux, as serial measurements of gastric bile acid concentrations were similar for the three meals. We conclude that the duodenal osmoreceptor mechanism is relatively insensitive to ethanol; that the relationship between energy density and gastric emptying rate does not hold in the case of ethanol; and that the gastro-oesophageal reflux which occurs in response to ethanol is not due to impairment of gastric emptying.

Adult↗

The baroreceptor mechanism for controlling renin secretion: effect of calcium channel blockers.

Renin secretion is inversely related to afferent arteriolar transmural pressure, or to some function of it such as stretch (the baroreceptor mechanism). It has been suggested that increased pressure depolarizes the renin-secreting juxtaglomerular cells, and that increased Ca influx through voltage-operated Ca channels mediates the inhibitory effect on renin secretion. If true, then Ca channel blockers should antagonize the inhibitory effect of increased pressure on renin secretion. To test this prediction, isolated rat kidneys were perfused with an oxygenated physiological salt solution in a single-pass system. Perfusate flow rate and renin concentration in the venous effluent were measured and their product, the renin secretory rate (RSR), was calculated. During the control period, increasing renal perfusion pressure (RPP) from 100 to 120 mm Hg decreased RSR to 42 +/- 5% of the control value. This inhibitory effect of increased RPP was blunted by 1 microM nifedipine, nearly blocked by 5 microM verapamil and completely blocked by 50 microM diltiazem. Inasmuch as nifedipine, verapamil and diltiazem are Ca channel blockers and because all three have been shown previously to block the inhibitory effect of depolarization on RSR, these results are consistent with the hypothesis that a depolarization-induced influx of Ca mediates the inhibitory effect of increased RPP on RSR.

Animals↗

[The effect of degree of renal function damage on the levels of serum gastrin and gastric acid secretion].

Fasting serum gastrin concentrations and both basal and maximum-stimulated gastric acid secretory rates have been studied in 225 patients with various degrees of impairment of renal function and 42 healthy subjects. Basal gastrin concentrations in the chronic renal failure (CRF) patients were significantly higher (p < 0.05) than in control subjects. When the glomerular filtration rate (GFR) was used as an index of the degree of renal impairment serum gastrin rose proportionately with the degree of renal failure. Basal (BAO), maximal (MAO) and peak acid output (PAO) in the CRF patients were significantly lower (p < 0.05) than in the control group. Both in the basal condition and during pentagastrin stimulation the CRF patients had low volume of gastric secretion. There was significant positive correlation between basal serum gastrin concentrations and the severity of renal damage. The basal serum gastrin concentration was inversely related to BAO, MAO and PAO in the CRF patients with severe impairment of renal functions. The results indicate that hypergastrinemia in CRF patients might be due to a combined effect of impaired renal catabolism of gastrin and overproduction of gastrin associated with hypochlorhydria. The present findings suggest that in CRF there are some unknown mechanisms that inhibit gastric secretion.

Adult↗

Electrolyte and protein secretion by the perfused rabbit mandibular gland stimulated with acetylcholine or catecholamines.

1. A method is described for the isolation and vascular perfusion in vitro of the mandibular gland of the rabbit. The perfusate is a physiological salt solution containing glucose as the only metabolic substrate.2. During perfusion with solutions containing acetylcholine, the gland secretes vigorously at a rate and in a manner similar to that seen in vivo. Although the gland becomes oedematous during perfusion, the extent of this oedema appears to have no influence on secretory ability: the perfused glands were capable of functioning for at least 4 h, and often for more than 6 h.3. Acetylcholine evoked a small secretory response at a concentration of 8 x 10(-9) mol l(-1) and a maximum response at 8 x 10(-7) mol l(-1). Eserine (2 x 10(-5) mol l(-1)) evoked secretory responses comparable to those evoked by acetylcholine in a concentration of 8 x 10(-9) mol l(-1). Secretion, whether unstimulated or evoked by acetylcholine or eserine, could be blocked completely by atropine.4. During prolonged stimulation with acetylcholine, the fluid secretory response declined rapidly over a period of about 15 min from an initial high value to a much lower plateau value. After 3 or more hours of stimulation, the secretory response began once more to decline, this time towards zero. If, before the second period of decline begins, stimulation is interrupted for about 30 min, the gland recovers its initial responsiveness to further stimulation with acetylcholine.5. The Na, K, Cl and HCO(3) concentrations and the osmolality of acetylcholine evoked saliva exhibited flow-dependency similar to that seen in vivo. The concentrations of Na and Cl, but not K and HCO(3), increased by about 25 mmol l(-1) during periods of prolonged stimulation with acetylcholine even though the salivary secretory rate was constant. The concentrations of K and HCO(3), but not Na and Cl, increased progressively as the concentration of infused acetylcholine was increased.6. Salivary protein secretion increased with increasing concentrations of acetylcholine to a greater extent than did fluid secretion. During continuous stimulation, the rate of protein secretion fell off much faster than the rate of fluid secretion.7. The beta-adrenergic agonist isoproterenol evoked a fluid secretory response only equal to about 5% of that evoked by acetylcholine, but still the response declined during continued stimulation. The electrolyte composition of isoproterenol-evoked saliva was vastly different from that evoked by acetylcholine, being particularly rich in K and HCO(3). The isoproterenol-evoked saliva was also extremely rich in protein so that the total protein secretion evoked by isoproterenol was much greater than that evoked by acetylcholine.8. The alpha-adrenergic agonist phenylephrine was without stimulatory effect on salivary fluid secretion and caused a reduction in the secretory response to acetylcholine. The drug had little or no effect on the electrolyte content of acetylcholine-evoked saliva and appeared to reduce its protein content.

Acetylcholine↗

C-peptide and insulin secretion. Relationship between peripheral concentrations of C-peptide and insulin and their secretion rates in the dog.

Estimation of the insulin secretory rate from peripheral C-peptide concentrations depends upon the following characteristics of C-peptide kinetics: (a) equimolar secretion of insulin and C-peptide by pancreatic beta cells; (b) negligible hepatic extraction of C-peptide; (c) constant metabolic clearance rate (MCR) of C-peptide over a physiological and pathophysiological range of plasma levels; and (d) proportional changes in the secretion rate of C-peptide and its peripheral concentrations under varying physiological conditions. In the present experiments, the relationship between a variable intraportal infusion of C-peptide and its concentration in the femoral artery was explored in 12 pancreatectomized dogs. As the infusion of C-peptide was rapidly increased, the magnitude of its peripheral concentration initially increased less than the infusion rate by 20-30%. After an equilibration period of approximately 30 min, however, further increases and decreases in the intraportal infusion were accompanied by nearly proportional changes in its peripheral concentration. Estimates of the amount of C-peptide infused during the experiment based on the steady state C-peptide MCR and its peripheral concentration were within 20% of the amount of C-peptide actually infused. These experiments demonstrate that the portal delivery rate of C-peptide can be calculated from its MCR and peripheral concentration in the dog. They also provide a basis for testing the validity of more complicated models of insulin secretion based on peripheral C-peptide concentrations in the dog as well as other species, including man. Finally, we have shown that the hepatic extraction of endogenously secreted C-peptide is negligible in the basal state (3.1 +/- 6.1%), and does not change after oral glucose ingestion. The MCR of exogenous dog C-peptide was similar whether measured by constant peripheral intravenous infusion (12.3 +/- 0.7 ml/kg per min), constant intraportal infusion (13.4 +/- 0.6 ml/kg per min), or analysis of the decay curve after a bolus injection (13.5 +/- 0.7 ml/kg per min).

Animals↗

In vivo dynamics of luteinizing hormone secretion and clearance in man: assessment by deconvolution mechanics.

The dynamics of LH secretion and clearance were studied in vivo in eight healthy young men using a novel multiple parameter deconvolution procedure to resolve underlying secretion and clearance rates simultaneously from serial serum immunoactive LH concentrations. This deconvolution analysis disclosed random LH secretory bursts occurring at a mean (+/- SEM) interpulse interval of 72 +/- 5 min. The frequency of these secretory bursts was 6.9 +/- 0.6 episodes/8 h. Each resolved LH secretory event had an average half-duration of only 7.8 +/- 0.5 min, which was remarkably shorter than the LH concentration peak duration of 60 +/- 6 min. The maximal LH secretory rate achieved within a secretory burst averaged 0.40 +/- 0.05 mIU/min.mL (0.14 IU/min.L), which corresponded to a mass of LH released of 3.2 +/- 0.3 mIU/mL distribution vol (IU/L). By linear regression analysis, both the maximal rate and mass of LH released per secretory burst were positively correlated with the duration of the subsequent interpulse interval (P less than 0.001). In physiological experiments, the mass of LH released per secretory burst was increased by iv GnRH injections or primary gonadal failure, and decreased by sc administration of a selective GnRH antagonist (Nal,Glu-GnRH). The mean endogenous LH production rate calculated by deconvolution [180 +/- 40 mIU/min (0.18 IU/min)] was not different from a nominal value of 228 +/- 80 mIU/min (0.228 IU/min) extrapolated from earlier steady state LH infusions. Deconvolution estimated single phase half-times of endogenous LH disappearance of 87 +/- 8 min, were in general harmony with values of 44-106 min obtained previously in four LH-deficient men injected with purified LH. Moreover, creation of synthetic LH series using our deconvolution estimates yielded 24-h LH pulse profiles similar quantitatively and qualitatively to those in normal men. In summary, we applied a new multiple parameter deconvolution procedure to immunoactive LH pulse profiles to discern the nature of physiological LH secretory events and estimate endogenous LH disappearance rates. These studies in normal men have revealed that 1) LH secretory bursts occur every 72 min; their mean half-duration is 7.8 min; and 3.2 mIU/mL (3.2 IU/L) are released per secretory peak; 2) amplitudes of in vivo LH secretory bursts are augmented in primary gonadal failure and/or by exogenous GnRH injections and attenuated by a GnRH antagonist; 3) the duration of a postsecretory pause is proportional to the amplitude of the preceding LH secretory burst; and (4) 95% of total daily LH release occurs in only 5 h/day.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

The secretory nerves of the parotid gland of the dog.

1. Secretory nerve fibres to the parotid gland of the dog have been found in the adventitia of the internal maxillary artery. In dogs under chloralose anaesthesia the course of these fibres from the mandibular nerve to the gland was determined by electrical stimulation at different sites. Secretion induced by these nerves was abolished by atropine but not by hexamethonium.2. In dogs in light barbiturate anaesthesia parotid secretion was evoked reflexly by pouring citric acid on the tongues. After division of the auriculo-temporal nerve and the nerves on the artery this secretion disappeared in about half the experiments and was greatly reduced in the others.3. The maximal secretory rate which could be obtained reflexly from the normally innervated parotid gland was first estimated in light barbiturate anaesthesia. Chloralose was then given and the auriculo-temporal nerve and the nerves on the artery were electrically stimulated together; in about half the experiments this could produce secretion at a rate as high as that obtained reflexly.4. By separate and simultaneous stimulation of different sets of nerve fibres convergence of the secretory fibres to the glandular cells could be demonstrated.5. It is concluded that a large number of post-ganglionic, cholinergic secretory fibres to the canine parotid gland run on the internal maxillary artery. In some dogs a small number of fibres seem to have escaped detection. Possibly they may reach the gland by way of the facial nerve.

Anesthesia↗

The secretion of electrolytes and enzymes by the pancreas of the anaesthetized cat.

1. The bicarbonate concentration in cat pancreatic juice falls and the chloride concentration increases at slow secretory rates. The concentration of sodium and potassium remain constant at all secretory rates.2. Acetazolamide reduces the maximal rate of secretion markedly, and the maximal bicarbonate concentration slightly, but does not alter the reciprocal relationship between bicarbonate and chloride at slow rates of flow.3. By perfusion of the main duct it has been shown that there is a loss of bicarbonate and a gain of chloride across the duct wall due to a passive process of exchange diffusion. It is suggested that this may account for a substantial part of the flow-dependent changes in bicarbonate and chloride concentrations in the intact gland.4. The enzyme content of pancreatic juice is made up of a small continuous basal output, to which may be added a much larger secretion in response to hormonal stimulation.5. From analysis of successive small samples of juice it has been found that the response to single injections of pancreozymin lasts a very short time, during which the secretory cells release enzymes in a small volume of chloride-containing fluid.6. It is concluded that in the cat pancreatic secretion consists of an isosmolar primary secretion mostly of sodium bicarbonate, to which is added small amounts of a chloride-containing enzyme secretion. This fluid is modified, particularly at slow flow rates, by transductal exchange of chloride and bicarbonate which, at least in the main duct, is passive in nature.

Acetazolamide↗

Concentration dependency of the renal vascular and renin secretory responses to adenosine receptor agonists.

Exogenous adenosine inhibits renin secretion and can either vasoconstrict or vasodilate the renal vasculature in vivo. In previous experiments, we found that micromolar concentrations of N6-cyclohexyl adenosine and 5'-N-ethylcarboxamide adenosine, analogs which are relatively selective for A1 and A2 adenosine receptors, respectively, tended to have opposite effects on both afferent arteriolar resistance and renin secretory rate in isolated rat kidneys perfused at constant pressure. Because the affinities of A1 and A2 receptors differ considerably, the purpose of the present experiments was to determine the concentration dependencies of the renal hemodynamic (perfusion pressure or perfusate flow, glomerular filtration rate, filtration fraction) and the renin secretory effects of adenosine, N6-cyclohexyl adenosine and 5'-N-ethylcarboxamide adenosine. Both the renovascular and the renin secretory effects of CHA were biphasic; at submicromolar concentrations, total and afferent arteriolar resistances were increased and renin secretion was inhibited. At higher concentrations, these effects were reversed or abolished. 5'-N-Ethylcarboxamide adenosine and adenosine decreased total and segmental (afferent and efferent) resistances and stimulated renin secretion. Taken together, the results are consistent with the suggestions that A1 and A2 receptors mediate inhibition and stimulation of renin secretion, that afferent arteriolar A1 and A2 receptors mediate constriction and dilation and that efferent arteriolar A2 receptors mediate dilation.

Adenosine↗

Influence of calcium and cyclic nucleotides on beta-adrenergic sweat secretion in equine sweat glands.

The effects of Ca2+, the cyclic nucleotides adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP), and other parameters of sweat secretion from single equine sweat glands were examined in vitro. Extracellular Ca2+, the Ca2+ ionophore A23187, and the Ca2+ channel antagonist verapamil were all without effect on sweat secretion. Prolonged rinsing of the glands in Ca2+-free Ringer solution with 5 mM ethylenediaminetetraacetic acid decreased the secretion to 30% of the control sweat rate in response to the beta-adrenergic agonist isoproterenol; the sweat response was restored upon adding Ca2+ to the Ringer. cAMP but not cGMP analogues were as effective in stimulating sweat rates as isoproterenol, which elicited maximal secretory rates in vitro. cAMP stimulation was not inhibited by the beta-adrenergic antagonist propranolol. Because the equine sweat gland is predominantly stimulated via the beta-adrenergic receptor, we conclude that cAMP is a principal intracellular messenger in coupling this type of stimulus to the fluid secretion response in this tissue.

Animals↗

Parotid function and composition of parotid saliva among elderly edentulous African-American diabetics.

This study examined parotid salivary flow rate and composition in three groups of differently treated diabetics and a control group of non-diabetics. The study population was composed of edentulous African-Americans at least 65 years of age. Group A was the control, Group B insulin-dependent (Regular Iletin, U-100 qd.), Group C controlled by oral medication (Tolbutamide, 500 mg qd.), and Group D was diet controlled. All diabetic patients had serum glucose values under 250 mg/dl. Salivary flow rates, secretory IgA, electrolytes (Na+, Cl-, K+, Ca++) and total protein concentrations were evaluated. The results showed no significant differences between groups with respect to salivary flow rates, electrolytes and IgA concentrations. Additionally, all diabetic groups demonstrated a significantly lower salivary total protein concentration when compared to the controls. There appears to be no evident decrease in salivary flow rate in these three differently controlled diabetic groups compared with healthy non-diabetics.

Aged↗

Pituitary thyrotropin (TSH) rebound phenomenon and kinetics of secretion in the goitrous rat: differential effects of thyroxine on synthesis and release of TSH.

The protein metabolism and [3H]-uridine uptake of thyroid and adenohypophysis and the kinetics of pituitary TSH rebound (PTR) were studied in goitrous female rats (fed propylthiouracil, PTU: for 7-12 weeks) following single, iv injections of L-thyroxine (T4: 0.8 to 200 mug). Goitrogenesis was associated with reduced protein concentration and enhanced uptake of [3H] uridine in both glands. Plasma levels of TSH were invariably elevated but stores in the adenohypophysis were consistently reduced. Small doses of T4 (4 mug) induced significant TSH repletion in the pituitary within 2-6 h following injection. Accumulations of pituitary TSH to supranormal levels (15-fold increases) were achieved with 20 mug T4 at 6 and 24 h; higher doses (100-200 mug) inhibited the PTR at all time intervals tested (0.5-24 h). Administration of puromycin or actinomycin D did not influence the PTR. Protein content and labeled uridine uptake of the pituitary bore no apparent relationship to T4-induced TSH repletion in the gland. Blood clearance rate of exogenous rat TSH was measured prior to and during PTR. Plasma half-life was determined to be 13.6 and 19.9 min in euthyroid and chronically hypothyroid rats, respectively; it was not significantly altered from the latter during rebound (18.7 min). Calculations of theoretical TSH secretory rates prior to (50.5 +/- 4.4 mU/h) and after rebound with 20 mug T4 (25.4 +/- 4.2 mU/H) revealed that the reaccumulation of TSH in the pituitary induced with T4 cannot be attributed solely to inhibition of release, but may also involve enhancement of synthesis. It is concluded that T4 administration at high dose levels inhibits both synthesis and release of TSH from pituitary thyrotrophs, whereas low critical doses of T4 suppress release, but augment synthesis and/or facilitate conformational change in a pituitary precursor(s) molecule which renders it detectable by bioassay.

Animals↗

[Pharmacological effects of piprozoline on bile secretion in dogs (author's transl)].

Ethyl (Z)-(3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)-acetate (piprozoline, Gö 919, Probilin) and its main metabolite Gö 3284 induce a strong choleretic effect in dogs after i.v. and i.d. administration as well. Intestinal absorption is fast, and already 3.5 min after administration of the substances a rise of the bile volume and of the optical density of the secreted bile can be observed. The secretion rates of bile solids and bile acids per time (min) increase almost at the same time, too. Moreover, piprozoline presumably stimulates the synthesis of bile acids and of the other matter in addition to the raised secretory rate. In the group of choleretics, piprozoline is to be placed among the cholepoietics. Under the influence of piprozoline and Gö 3284, the content of solids sometimes decreases for a short period immediately after administration of substances. A strong linear correlation occurs between the secretion rate of bilirubin and bile acids. The increase of bile volume under the influence of piprozoline and Gö 3284 may be seen as osmotic effects caused by the stimulation of the bile acid dependent and the bile acid independent (Na+-ion dependent) canalicular mechanisms of choleresis.

Alkaline Phosphatase↗