PACAP-(1-38) as neurotransmitter in the porcine adrenal glands.
The concentration of pituitary adenylyl cyclase-activating polypeptide [PACAP-(1-38)] in porcine adrenal glands amounted to 14 +/- 3 pmol/g tissue. PACAP immunoreactive (PACAP-IR) fibers innervated adrenal chromaffin cells (often co-localized with choline acetyltransferase). Subcapsular fibers traversed the cortex-innervating endocrine cells and blood vessels [some co-storing mainly calcitonin gene-related peptide but also vasoactive intestinal polypeptide (VIP)]. PACAP-IR fibers were demonstrated in the splanchnic nerves, whereas IR adrenal nerve cell bodies were absent. In isolated, vascularly perfused adrenal gland, splanchnic nerve stimulation (16 Hz) and capsaicin (10(-5) M) increased PACAP-(1-38) release (1.6-fold and 6-fold respectively, P = 0.02). PACAP-(1-38) dose-dependently stimulated cortisol (2 x 10(-10) M; 24-fold increase, P = 0.02) and chromogranin A fragment (2 x 10(-9) M; 15-fold increase, P = 0.05) secretion. Both were strongly inhibited by the PAC(1)/VPAC(2) receptor antagonist PACAP-(6-38) (10(-7) M). PACAP-(6-38) also inhibited splanchnic nerve (10 Hz)-induced cortisol secretion but lacked any effect on splanchnic nerve-induced pancreastatin secretion. PACAP-(1-38) (2 x 10(-10) M) decreased vascular resistance from 5.5 +/- 0.6 to 4.6 +/- 0.4 mmHg. min. ml(-1). PACAP-(6-38) had no effect on this response. We conclude that PACAP-(1-38) may play a role in splanchnic nerve-induced adrenal secretion and in afferent reflex pathways.
Tornøe
K
K
Department of Medical Physiology, The Panum Institute, University of Copenhagen DK 2200, Denmark.
Hannibal
J
J
Jensen
T B
TB
Georg
B
B
Rickelt
L F
LF
Andreasen
M B
MB
Fahrenkrug
J
J
Holst
J J
JJ
D000311:Adrenal Glands / Q000737:chemistry* / Q000294:innervation*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D053379:Chromogranin A; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006854:Hydrocortisone / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009412:Nerve Fibers / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000032:analysis* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010187:Pancreatic Hormones / Q000032:analysis / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis* / Q000235:genetics / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000032:analysis; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000235:genetics; D013153:Splanchnic Nerves / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D053379:Chromogranin A; D009479:Neuropeptides; D010187:Pancreatic Hormones; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; C108046:pituitary adenylate cyclase-activating-peptide (1-38), pig; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); C050836:pancreastatin; D014660:Vasoactive Intestinal Peptide; D002211:Capsaicin; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine