Prostaglandin E2 inhibits Na-K-2Cl cotransport in medullary thick ascending limb cells.

Prostaglandin E2 (PGE2) is known to inhibit transepithelial Cl transport in medullary thick ascending limb (mTAL), but the mechanism of inhibition or the transport pathway affected has not been identified. We undertook this study to examine the effect of PGE2 on Na-K-2Cl cotransport in mouse mTAL cells in culture. In nanomolar concentrations, PGE2 inhibited the Na- and Cl-dependent, bumetanide-sensitive K influx by 45%, and this inhibition was also observed in the presence of 3 mM ouabain. Although PGE2 also inhibited ouabain-sensitive K flux, that inhibition was abolished in the presence of apical nystatin, suggesting that the pump inhibition was secondary to diminished Na entry into the cells. The effect of PGE2 was concentration dependent. Inhibition was observed at a concentration of < 1 nM, and half-maximal effect was observed at 2.5 nM. The effect of PGE2 was not mediated by an action on cytosolic Ca because cytosolic Ca was unchanged after the addition of PGE2. PGE2 reduced the maximal velocity for the cotransporter but had no effect on the affinity of the cotransporter for external Na, K, or Cl. Specific [3H]bumetanide binding was reduced in the presence of PGE2, suggesting that PGE2 affected bumetanide-sensitive K influx by downregulating the number of functioning Na-K-2Cl cotransporters. These results suggest that Na-K-2Cl cotransport in the mTAL cells may be under tonic inhibitory control of PGE2.

A mathematical model relating cohort and period mortality.

This paper presents a mathematical model for changing mortality in functional form. This model may be used to obtain cohort forces of mortality and cohort survivorship functions from a period force of mortality and a period life table under conditions of gradually changing mortality if an estimate of the amount of change in mortality is available. An example is given to show how the cohort functions are derived from the period functions.

Control of pineal indole biosynthesis by changes in sympathetic tone caused by factors other than environmental lighting.

The melatonin (5-methoxy-N-acetylserotonin) content and N-acetyltransferase activity of rat pineal increase rapidly in response to physical immobilization or insulin-induced hypoglycemia. Carbohydrate consumption, which causes insulin release without hypoglycemia, does not elicit these pineal responses. Prior treatment with propranolol, a beta-adrenergic blocking agent, inhibits the N-acetyltransferase responses to hypoglycemia and immobilization, indicating that these changes result from stimulation of pineal beta-receptors by a catecholamine, presumably norepinephrine released from pineal sympathetic nerve terminals. Prior destruction of those terminals with 6-hydroxydopamine does not block, but actually potentiates, the increase in melatonin content and N-acetyltransferase activity after induced hypoglycemia or immobilization. This finding probably reflects an action of circulating catecholamines, secreted from the adrenal medullae or surviving sympathetic nerve terminals, on supersensitive pineal cells. These observations indicate that factors other than changes in environmental lighting, which modify sympathetic nervous tone, can also influence pineal function.