Studies on the mechanism of renin release from isolated superfused rat glomeruli: effects of calcium, calcium ionophore and lanthanum

Abstract

SUMMARY1. The effects of external medium calcium concentration, the ionophore A23187 and lanthanum on the rate of renin release in vitro were studied with particular emphasis on results obtained from isolated superfused glomeruli of rat kidneys.2. The response to reduction in superfusate calcium concentration from 2 mm was a graded and reversible increase in the rate of renin release. An increase in release was detectable at 02 mm calcium; a threefold increase was found 36 mm after a change from 2 mm calcium to calcium-free superfusate. A similar relative increase in release resulted from reductions from 0-1 mm to zero calcium, but the absolute amounts of renin released were greater in this latter series. Renin release from kidney cortical slices similarly increased in response to calcium-free incubation medium.3. The effects of A23,87 on renin release were modest. Changing from 2 mm calcium during control periods to calcium-free Ringer with A23187 added caused an attenuated and more delayed increase in release than the change to calcium-free Ringer without ionophore. This difference in response was abolished when glomeruli were superfused with 0.1 mM calcium during the preceding 1 hr control period. There was no significant difference in renin release from glomeruli exposed to calcium-free EGTARinger with and without A23187 in the 2 mm calcium series; in the 0.1 mm calcium series the increase in release following a shift to calcium-free EGTA-containing superfusate with A23187 added was significantly greater than in the absence of the ionophore.4. Addition of lanthanum (1 or 0 05 mM) to calcium-containing as well as calcium-free superfusate resulted in a significant depression of renin Some of the present data were presented in preliminary form at the VIth Int. Nephrol. Congress, Florence, 1975. Abstracts free communications no. 518. L. BAUMBACH AND P. P. LEYSSAC release. Subsequent removal of the lanthanum did not restore the rate of release unless EGTA was added; in the latter case a massive increase in renin release occurred resulting in a marked depletion of the remaining renin content of the glomeruli.5. It is concluded that calcium influences renin release by a direct action on the juxtaglomerular cells. The data support the previous suggestion that basal renin release is a function of active, calcium-dependent cell volume regulation -swelling causing an increase in the release; and further suggest that membrane-bound calcium has a direct effect on the cell membrane permeability to renin.6. The results exclude that calcium-stimulated exocytosis is responsible for basal renin release from the juxtaglomerular cells adhering to isolated glomeruli.

Renin release from isolated rat glomeruli: seasonal variations and effects of D600 on the response to calcium deprivation.

“…Increased renin release due to a decrease in membrane bound calcium does not necessarily contradict previous results (Baumbach & Leyssac, 1977) which showed that addition ofthe ionophore A23187 to a calcium free medium reduced renin release. This reduction could be due to an increased delivery of calcium from intracellular stores to the outside, counteracting the decrease of membrane-bound calcium.…”

“…Thus, acute exposure to a calcium-free extracellular fluid causes an increase in renin release both from the isolated perfused intact kidney and from cortical slices and isolated glomeruli in vitro (Vandongen & Peart 1974;Baumbach & Leyssac 1977;Fray 1977;Harada, Lester & Rubin 1979). However a transient increase in renin release following addition of calcium to the perfusate after prolonged exposure to calcium-free medium has also been reported (Lester & Rubin 1977;Chen & Poisner 1976).…”

Renin release from isolated rat glomeruli: effects of colchicine, vinca alkaloids, dimethylsulphoxide, and cytochalasins.

“…The results obtained are consistent with our previous observations (Baumbach & Leyssac, 1977) indicating that the process of renin release from isolated glomeruli is different from an exocytotic process, but is related to cell volume.…”

“…No experimental evidence for an effect on transmembrane calcium flux has been provided, but if the cytochalasins do actually interfere with calcium influx such an effect could explain the observed increase in osmotically provoked renin release by interference with cell volume regulation (cf. Baumbach & Leyssac, 1977).…”

“…Ultrastructural studies on the juxtaglomerular apparatus have revealed the presence of both microtubules and microfilaments in the renin containing cells (Peter, 1976) leading to the assumption that the exocytotic mode of secretion also applies to renin release from the juxtaglomerular cells. However, actual fusion of granules with the plasma membrane has never been observed in this structure (Lee, Hurley & Hopper, 1966;Peter, 1976) and recent evidence on the action of calcium on renin release (Vandongen & Peart, 1976;Watkins, Davis, Lohmeier & Freeman, 1977;Baumbach & Leyssac, 1977) has been difficult to reconcile with the concept of exocytosis.…”