title: Aluminium-induced changes of fusion pore properties attenuate prolactin secretion in rat pituitary lactotrophs.
abstract: Hormone secretion is mediated by Ca(2+)-regulated exocytosis. The key step of this process consists of the merger of the vesicle and the plasma membranes, leading to the formation of a fusion pore. This is an aqueous channel through which molecules stored in the vesicle lumen exit into the extracellular space on stimulation. Here we studied the effect of sub-lethal dose of aluminium on prolactin secretion in isolated rat pituitary lactotrophs with an enzyme immunoassay and by monitoring electrophysiologically the interaction of a single vesicle with the plasma membrane in real time, by monitoring membrane capacitance. After 24-h exposure to sub-lethal AlCl(3) (30 μM), the secretion of prolactin was reduced by 14±8% and 46±11% under spontaneous and K(+)-stimulated conditions, respectively. The frequency of unitary exocytotic events, recorded by the high-resolution patch-clamp monitoring of membrane capacitance, a parameter linearly related to the membrane area, under spontaneous and stimulated conditions, was decreased in aluminium-treated cells. Moreover, while the fusion pore dwell-time was increased in the presence of aluminium, the fusion pore conductance, a measure of fusion pore diameter, was reduced, both under spontaneous and stimulated conditions. These results suggest that sub-lethal aluminium concentrations reduce prolactin secretion downstream of the stimulus secretion coupling by decreasing the frequency of unitary exocytotic events and by stabilizing the fusion pore diameter to a value smaller than prolactin molecule, thus preventing its discharge into the extracellular space.
authors: Departamento de Biologia and CESAM, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors: A I
authors: AI
authors: Calejo
authors: J
authors: J
authors: Jorgačevski
authors: V S
authors: VS
authors: Silva
authors: M
authors: M
authors: Stenovec
authors: M
authors: M
authors: Kreft
authors: P P
authors: PP
authors: Gonçalves
authors: R
authors: R
authors: Zorec
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects*; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology*; D025802:Electric Capacitance; D004558:Electric Stimulation; D005089:Exocytosis / Q000187:drug effects; D052682:Lactotrophs / Q000187:drug effects*; D008297:Male; D008561:Membrane Fusion / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D000077410:Aluminum Chloride; D011388:Prolactin