Pituitary adenylate cyclase activating polypeptide (PACAP) in the gastrointestinal tract of the rat: distribution and effects of capsaicin or denervation.
The expression of pituitary adenylate cyclase activating polypeptide (PACAP) was studied in the gastrointestinal tract (GI-tract) of normal rats using radioimmunoassay, chromatography, immunocytochemistry, and in situ hybridization. PACAP-38, PACAP-27, and PACAP-related peptide were demonstrated in all parts of the GI-tract, PACAP-38 being the predominant form confirmed by chromatography. PACAP-immunoreactive nerve fibers and nerve cell bodies were found in the myenteric ganglia throughout the GI-tract. PACAP-containing nerve cell bodies were also demonstrated in the submucous ganglia of the small and large intestine. The synthesis of PACAP in intrinsic neurons was confirmed by in situ hybridization. Double immunostaining showed that PACAP is present in calcitonin gene-related peptide-containing sensory nerve fibers as well as in vasoactive intestinal polypeptide (VIP)- or VIP/gastrin-releasing peptide (GRP)-containing (intramural) nerve fibers in the upper GI-tract and in anally projecting, intrinsic VIP-and VIP/nitric oxide syntase-containing nerve cell bodies and nerve fibers in the small and large intestine. Neonatal treatment with capsaicin significantly reduced the concentration of PACAP-38 in the esophagus, stomach, and colon. Extrinsic denervation decreased the PACAP-38 concentration in the stomach, while no change was observed in the small intestine. These results indicate that PACAP- immunoreactive nerve fibers in the GI-tract originate from both intrinsic (enteric) and extrinsic (presumably sensory) sources suggesting that PACAP may have diverse gastrointestinal functions.
Hannibal
J
J
Department of Clinical Biochemistry, University of Copenhagen, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. biochbbh@inet.uni-c.dk
Ekblad
E
E
Mulder
H
H
Sundler
F
F
Fahrenkrug
J
J
D000818:Animals; D000831:Animals, Newborn; D017763:Autonomic Denervation; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000235:genetics; D002211:Capsaicin / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004064:Digestive System / Q000294:innervation*; D017615:Enteric Nervous System / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D004947:Esophagus / Q000294:innervation; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization; D007420:Intestine, Large / Q000294:innervation; D007421:Intestine, Small / Q000294:innervation; D009412:Nerve Fibers / Q000737:chemistry; D009475:Neurons, Afferent / Q000737:chemistry / Q000648:ultrastructure; D009479:Neuropeptides / Q000032:analysis / Q000235:genetics*; D018377:Neurotransmitter Agents / Q000032:analysis / Q000235:genetics*; D010446:Peptide Fragments / Q000032:analysis / Q000235:genetics; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010902:Pituitary Gland / Q000737:chemistry / Q000187:drug effects*; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013270:Stomach / Q000294:innervation; D014660:Vasoactive Intestinal Peptide / Q000032:analysis / Q000235:genetics
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D018377:Neurotransmitter Agents; C108999:PACAP-related peptide; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011498:Protein Precursors; D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin