Pituitary adenylate cyclase-activating polypeptide stimulates both adrenocortical cells and chromaffin cells in the frog adrenal gland.
In a previous report, we have shown that frog pituitary adenylate cyclase-activating polypeptide (fPACAP38) is a potent stimulator of corticosteroid secretion by frog adrenal slices in vitro. The aim of the present study was to determine the mode of action of PACAP on the frog adrenal gland. Immunoelectron microscopic labeling revealed that PACAP-like immunoreactivity is present in electron-dense vesicles within nerve endings located in the vicinity of both adrenocortical and chromaffin cells. Exposure of dispersed adrenal cells to fPACAP38 caused stimulation of corticosteroid secretion. Labeling of cultured adrenal cells with [125I]PACAP27 revealed the existence of PACAP-binding sites on both adrenocortical and chromaffin cells. Saturation and competition experiments showed the occurrence of high affinity and selective receptors for fPACAP38 on cultured adrenal cells. fPACAP38 (10(-8)-10(-5) M) provoked a dose-dependent stimulation of cAMP production by frog adrenal slices. Microflurimetric studies demonstrated that fPACAP38 induced a substantial elevation of the intracellular calcium concentration in both adrenocortical and chromaffin cells. The present results indicate that in the frog adrenal gland, PACAP fibers innervate both adrenocortical and chromaffin cells. The data show the presence of PACAP receptors on the two cell types. PACAP exerts a direct stimulatory effect on corticosteroid-producing cells. This effect is probably mediated through stimulation of adenylyl cyclase activity and/or augmentation of intracellular Ca2+. PACAP also increases intracellular Ca2+ in chromaffin cells. These data suggest that PACAP, released locally in the adrenal gland, acts as a neuroendocrine factor, regulating the activity of adrenocortical and chromaffin cells.
Yon
L
L
European Institute for Peptide Research, Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U-413, UA CNRS, University of Rouen, Mont-Saint-Aignan, France.
Chartrel
N
N
Feuilloley
M
M
De Marchis
S
S
Fournier
A
A
De Rijk
E
E
Pelletier
G
G
Roubos
E
E
Vaudry
H
H
D000302:Adrenal Cortex / Q000166:cytology / Q000502:physiology*; D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000311:Adrenal Glands / Q000166:cytology / Q000502:physiology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000502:physiology*; D000242:Cyclic AMP / Q000096:biosynthesis; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011895:Rana ridibunda; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000378:metabolism; D014018:Tissue Distribution
D000305:Adrenal Cortex Hormones; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D000242:Cyclic AMP; D002118:Calcium