Inhibition of atrial peptide secretion at different stages of the secretory process: Ca2+ dependence.
We have used a noncontracting in vitro preparation of stretched and unstretched rat atria to estimate contributions of constitutive and regulated pathways to the rates of stretch-augmented and basal secretion of immunoreactive atrial natriuretic peptide (ANP) and to examine effects of inhibition of the secretory sequence by 1) protein synthesis inhibitors, 2) disruption of forward vesicular traffic between endoplasmic reticulum and Golgi with brefeldin A (BFA, and 3) cellular ATP depletion. Protein synthesis inhibition with cycloheximide for 44 min slowed neither basal nor stretch-augmented ANP secretion but instead accelerated stretch-augmented secretion at low (but not at physiological) external Ca2+ concentration, suggesting that the constitutive component does not contribute substantially to either basal or stretch-augmented secretion. BFA, which disassembled Golgi cisternae, increased the stretch-augmented secretory rate via the regulated pathway and prevented Ca(2+)-dependent inactivation with time. Cellular ATP depletion rapidly and completely inhibited stretch-augmented secretion. We conclude that both basal and stretch-augmented utilize the energy-dependent regulated pathway, drawing on a large reservoir of concentrated prohormone stored in granules that is not detectably depleted during 44 min of stretch-augmented secretion at 37 degrees C.
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Department of Medicine, University of Chicago, Illinois 60637.
Upshaw-Earley
J
J
Goings
G E
GE
Hanck
D A
DA
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D020126:Brefeldin A; D002118:Calcium / Q000378:metabolism*; D003517:Cyclopentanes / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008854:Microscopy, Electron; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D003517:Cyclopentanes; D011500:Protein Synthesis Inhibitors; D020126:Brefeldin A; D009320:Atrial Natriuretic Factor; D002118:Calcium