Abstract
Secretory vesicles isolated from a variety of mammalian tissues are known to lyse and thereby release their secretory products when exposed to ATP. This process, which will be termed ATP‐induced lysis, has been studied most extensively using adrenal chromaffin‐granule preparations. We report here that ATP causes the lysis of a highly purified preparation of rat parotid secretory granules. The rate of granule lysis was measured spectrophotometrically, and ATP‐induced lysis was expressed as the increase in the rate of lysis (r = % lysis per min) when ATP was added. This lytic process was characterized with respect to pH, temperature, osmolarity, and the ionic composition of the media ATP‐induced lysis of parotid granules was found to have the following properties in common with the extensively characterized chromaffin‐granule process:
It is a saturable function of ATP with half‐maximal rates observed at 0.5 ± 0.1 mM ATP.
It is temperature dependent, eg, r = 6.1 ± 2.1%/min at 30°C vs 12.2 ± 2.5%/min at 37°C.
It is inhibited in hyperosmotic media, eg, r = 5.3 ± 0.3%/min at 0.3 OsM vs 0.8 ± 0.2%/min at 0.4 OsM.
It shows a nucleotide preference of ATP = GTP > ADP > AMP > CTP = ITP.
It has an anion requirement.
The above findings, combined with reports of ATP‐induced lysis of cholinergeric, insulin, and posterior‐pituitary vesicles, imply that ATP‐induced lysis may reflect an ATP‐dependent property of all secretory vesicles, and as such, this vesicle property could play a similar role in each exocytotic release process. Using a model system, Miller and Racker [22] made a surprising finding that the extent to which liposomes fuse with a black lipid membrane depends on the osmotic gradient across the vesicle membrane. In view of the osmotic dependence of ATP‐induced lysis in this and other secretory‐vesicle preparations, we postulate that ATP may prime secretory vesicles for fusion with the plasma membrane by inducing and/or maintaining an osmotic gradient across the vesicle membrane.