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Biomedical subjects

J N Forrest

Publications and source records attributed to J N Forrest.

At least 55 records · Page 3Linked to original sources
PubMed1980

Somatostatin: occurrence in urinary bladder epithelium and renal tubules of the toad, Bufo marinus.

Immunohistochemical techniques were used to detect immunoreactive somatostatin-like material in toad urinary bladder epithelium and in kidney distal tubules and collecting ducts. This material has immunological and chromatographic properties identical to those of synthetic cyclic somatostatin. The occurrence of somatostatin-like material in antidiuretic hormone-sensitive portions of the renal urinary system suggests a local regulatory or paracrine role for somatostatin.

Animals↗
PubMed1980

Somatostatin: an endogenous peptide in the toad urinary bladder inhibits vasopressin-stimulated water flow.

Somatostatin (somatotropin release-inhibiting factor; SRIF) is a tetradecapeptide present in brain, pancreas, gastrointestinal tract, and thyroid that inhibits the secretion or action of several hormones in these tissues. We observed that the toad urinary bladder contains concentrations of endogenous somatostatin (8.0 pg/micrograms of protein) comparable to those found in the mammalian pancreas and gastrointestinal tract. To determine if somatostatin directly alter the action of vasopressinn we studied the effects of this polypeptide on vasopressin-stimulated transport processes in the toad urinary bladder in vitro. Somatostatin produced a dose-dependent, reversible inhibition of vasopressin-stimulated osmotic water flow; it inhibited theophylline-stimulated osmotic water flow but not the water flow stimulated by 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate. These data are consistent with an inhibition of both basal and hormone-stimulated adenylate cyclase. Vasopressin-stimulated short circuit current was not inhibited by somatostatin. These studies provide direct evidence for an effect of somatostatin on hormone-modulated epithelial transport in tissues other than the gastrointestinal tract. We propose that endogenous somatostatin may function as a local regulator of the cellular action of vasopressin on osmotic water flow.

Animals↗
PubMed1979

Dissociation between plasma, urine, and renal papillary cyclic AMP content following vasopressin and DDAVP.

The effects of in vivo physiologic doses of vasopressin and 1-deamino-8-D-arginine vasopressin (DDAVP) on the cyclic AMP content of plasma, urine, and renal papillary tissue were determined in the ADH-deficient Brattleboro rat. During clearance studies, plasma cyclic AMP concentrations and both total and nephrogenous urinary cyclic AMP excretion in vasopressin- and DDAVP-treated rats were similar to the values in time-matched controls. In contrast, in situ renal papillary cyclic AMP content was higher (P less than 0.001) in both vasopressin- (35.7 +/- 3.6 pmol/mg protein) and DDAVP- (29.7 +/- 2.2 pmol/mg protein) treated rats compared to controls (15.1 +/- 1.3 pmol/mg protein). Endogenous stimulation of vasopressin by dehydration in normal rats increased both papillary cyclic AMP content (27.1 +/- 2.7 pmol/mg protein) and urine osmolality, whereas no change in papillary cyclic AMP was observed following dehydration in Brattleboro rats (13.6 +/- 0.8 pmol/mg protein) despite an increase in urine osmolality. The results demonstrate that changes in cyclic AMP following in vivo vasopressin are best demonstrated by measurement of in situ cyclic AMP content of the renal papilla, whereas total urinary cyclic AMP and nephrogenous cyclic AMP are not useful indices of tubular sensitivity to this hormone.

Animals↗
PubMed1978

Micropuncture study on the effects of lithium on proximal and distal tubule function in the rat kidney.

Micropuncture studies were performed in rats infused with LiCl to induce stable plasma lithium concentrations of 2--3 mEq/l, or with an equivalent amount of NaCl. In free flow experiments LiCl reduced proximal tubule fractional reabsorption of sodium and potassium. Reduced reabsorption of bicarbonate, as reflected by a decrease in TF/PCl, was also observed. Proximal fractional reabsorption of chloride, however, was not affected. The TF/PIn at the end proximal tubule was 2.6 +/- 0.2 (mean +/- SEM) in controls and 2.1 +/- 0.1 in the experimental animals (P less than 0.025). In the distal portions of the nephron lithium treatment caused a fall in fractional reabsorption of water and sodium, while potassium secretion was stimulated in the distal tubule. Previous studies have indicated that lithium influences antidiuretic hormone stimulated water transport in the collecting duct. These experiments demonstrate that lithium also affects the transport of water and electrolytes in multiple nephron segments, including the proximal and distal convolution.

Animals↗
PubMed1978

Superiority of demeclocycline over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone.

We evaluated demeclocycline and lithium therapy in 10 patients with the syndrome of inappropriate secretion of antidiuretic hormone. Despite severe water restriction, all patients had hyponatremia (mean +/- S.E.M. serum sodium of 122 +/- 1.1 meq per liter) and elevated urine osmolality (744 +/- 59 mOsm per kilogram) before treatment. Demeclocycline (600 to 1200 mg daily) restored serum sodium concentration to 139 +/- 1.1 meq per liter within five to 14 days, permitting unrestricted water intake in all patients. In three patients given lithium carbonate (900 mg daily) the serum sodium concentration, urine osmolality and urine volume were unchanged; since two patients had adverse central-nervous-system symptoms during lithium therapy, further study of this agent was abandoned. A patient with an unusual 22-year history of the syndrome was unresponsive to lithium, whereas long-term treatment with demeclocyline was markedly effective. Demeclocycline is superior to lithium in the treatment of the syndrome and may obviate the need for severe water restriction.

Adult↗
PubMed1977

Mechanism of active chloride secretion by shark rectal gland: role of Na-K-ATPase in chloride transport.

The isolated rectal gland of Squalus acanthias was stimulated to secrete chloride against an electrical and a chemical gradient when perfused in vitro by theophylline and/or dibutyryl cyclic AMP. Chloride secretion was depressed by ouabain which inhibits Na-K-ATPase. Thiocyanate and furosemide also inhibited chloride secretion but ethoxzolamide, a carbonic anhydrase inhibitor, did not. Chloride transport was highly dependent on sodium concentration in the perfusate. The intracellular concentration of chloride averaged 70-80 meq/liter in intact glands, exceeding the level expected at electrochemical equilibrium and suggesting active transport of chloride into the cell. These features suggest a tentative hypothesis for chloride secretion by the rectal gland in which the uphill transport of chloride into the cytoplasm is coupled through a membrane carrier to the downhill movement of sodium along its electrochemical gradient. The latter is maintained by the Na-K-ATPase pump while chloride is extruded into the duct by electrical forces.

Adenosine Triphosphatases↗
PubMed1976

Kidney transplant biopsies in the diagnosis and management of acute rejection reactions.

In 68 consecutive renal transplant biopsies, histopathologic changes and clinical status of the graft recipient, both at the time of biopsy as well as one month later, were evaluated by independent observers. Nine histologic features were graded semiquantitatively (scale, 0 to 4): glomerular endothelial swelling, proliferation, exudation and necrosis; interstitial edema and infiltrate: vascular endothelial edema, infiltration and necrosis. The total score for each biopsy was termed the acute rejection index (ARI). The validity of the ARI as a means of evaluation rejection reactions was established by correlating the ARI with a second, overall histopathologic categorization. Clinical status at the time of biopsy was classified by retrospective analysis of all clinical data except the biopsy. The mean ARI of patients with an acute clinical rejection was significantly higher than those of patients with just a chronic clinical rejection or no clinical rejection. The utility of the biopsy in predicting the response of the graft recipient to therapy was evaluated in those 46 patients in whom an acute rejection was diagnosed clinically and in whom a full and complete course of therapy for the acute clinical rejection was given. Of the 28 patients whom the pathologist predicted would response to therapy, 27 did show substantial improvement of their renal function up to one month following institution of treatment. Of the 18 patients whom the pathologist predicted would not respond to therapy, 15 had no clinical response. The data suggest that the transplant biopsy is helpful in 1) establishing the diagnosis of an acute rejection and 2) indicating whether or not the graft recipient will respond to standard immunosuppressive treatment for an acute rejection,

Acute Disease↗
PubMed1975

Effect of lithium on water and electrolyte metabolism.

Studies were performed in the rat to determine the effect of lithium on electrolyte transport in distal portions of the nephron since steep corticomedullary gradient for lithium has been demonstrated and ionic competition and/or substitution of lithium for sodium and potassium may play a role in inhibition of vasopressin-induced water transport. During the intravenous infusion of LiC1, in the absence of volume expansion and at plasma levels of 2-5 mequiv/liter of Li, maximum urine con-entration was inhibitied. Under the same conditions lithium administration impaired potassium secretion and urinary acidification and resulted in a natriuresis. These results indicate that lithium affects electrolyte transport in the same nephron segments in which the action of vasopressin is inhibitied. In addition, evidence is provided that suggests that during the chronic administration of LiC1, the sustained increase in oral intake of water and urinary flow rate results from an increase in thirst as well as reduced renal concentrating ability.

Animals↗
PubMed1974

On the mechanism of lithium-induced diabetes insipidus in man and the rat.

The mechanism of lithium-induced diabetes insipidus was investigated in 96 patients and in a rat model. Polydipsia was reported by 40% and polyuria (more than 3 liter/day) by 12% of patients receiving lithium. Maximum concentrating ability after dehydration and vasopressin was markedly impaired in 10 polyuric patients and was reduced in 7 of 10 nonpolyuric patients studied before and during lithium therapy. Severe polyuria (more than 6 liter/day) was unresponsive to trials of vasopressin and chlorpropamide, but improved on chlorothiazide. Rats receiving lithium (3-4 meq/kg/day) developed massive polyuria that was resistant to vasopressin, in comparison to rats with comparable polyuria induced by drinking glucose. Analysis of renal tissue in rats with lithium polyuria showed progressive increase in the concentration of lithium from cortex to papilla with a 2.9-fold corticopapillary gradient for lithium. The normal corticopapillary gradient for sodium was not reduced by lithium treatment. The polyuria was not interrupted by brief intravenous doses of vasopressin (5-10 mU/kg) or dibutyryl cyclic AMP (10-15 mg/kg) capable of reversing water diuresis in normal and hypothalamic diabetes insipidus rats (Brattleboro strain). The present studies suggest that nephrogenic diabetes insipidus is a common finding after lithium treatment and results in part from interference with the mediation of vasopressin at a step distal to the formation of 3',5' cyclic AMP.

Animals↗