Role of cyclic AMP and Ca2+ in potentiation of rat lacrimal gland protein secretion.
Addition of a cholinergic agonist carbachol and vasoactive intestinal peptide (VIP) to dispersed rat exorbital lacrimal gland acini produces protein secretion, measured by secretion of the enzyme peroxidase, that was statistically significantly greater than additive (potentiated). To determine where in stimulus-secretion coupling these secretagogues interact to potentiate secretion, rat exorbital gland acini were incubated simultaneously with cyclic AMP- and Ca2+-dependent agonists and protein secretion, cyclic AMP level, or Ca2+ concentration measured. As a measure of protein secretion, the supernatant obtained after centrifugation of acini was analyzed for peroxidase, a protein secreted by rat lacrimal glands. Interaction did not occur at the receptor level, because peroxidase secretion also was potentiated by simultaneous addition of carbachol and forskolin, which activates the catalytic subunit of adenyl cyclase. A potentiated increase in the cyclic AMP level did not potentiate protein secretion, because the level was the same with VIP as with carbachol and VIP added together at concentrations that potentiated peroxidase secretion. A potentiated increase in free intracellular [Ca2+] did not potentiate protein secretion, because [Ca2+] was greater with carbachol than with carbachol and VIP added together at concentrations that potentiated peroxidase secretion. We conclude that cholinergic- and VIP-dependent pathways interact to potentiate lacrimal gland protein secretion after the rise of intracellular cyclic AMP or Ca2+.
Dartt
D A
DA
Immunology Unit, Eye Research Institute, Boston, MA 02114.
Baker
A K
AK
Rose
P E
PE
Murphy
S A
SA
Ronco
L V
LV
Unser
M F
MF
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004357:Drug Synergism; D007477:Ions; D007765:Lacrimal Apparatus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D007477:Ions; D011506:Proteins; D014660:Vasoactive Intestinal Peptide; D002217:Carbachol; D000242:Cyclic AMP; D009195:Peroxidase; D002118:Calcium