Regulation of atrial natriuretic peptide secretion by cholinergic and PACAP neurons of the gastric antrum.
Atrial natriuretic peptide (ANP) released from enterochromaffin cells helps regulate antral somatostatin secretion, but the mechanisms regulating ANP secretion are not known. We superfused rat antral segments with selective neural agonists/antagonists to identify the neural pathways regulating ANP secretion. The nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) stimulated ANP secretion; the effect was abolished by hexamethonium but doubled by atropine. Atropine's effect implied that DMPP activated concomitantly cholinergic neurons that inhibit and noncholinergic neurons that stimulate ANP secretion, the latter effect predominating. Methacholine inhibited ANP secretion. Neither bombesin nor vasoactive intestinal polypeptide stimulated ANP secretion, whereas pituitary adenylate cyclase-activating polypeptide (PACAP)-27, PACAP-38, and maxadilan [PACAP type 1 (PAC1) agonist] each stimulated ANP secretion. The PAC1 antagonist M65 1) abolished PACAP-27/38-stimulated ANP secretion; 2) inhibited basal ANP secretion by 28 +/- 5%, implying that endogenous PACAP stimulates ANP secretion; and 3) converted the ANP response to DMPP from 109 +/- 21% above to 40 +/- 5% below basal, unmasking the cholinergic component and indicating that DMPP activated PACAP neurons that stimulate ANP secretion. Combined atropine and M65 restored DMPP-stimulated ANP secretion to basal levels. ANP secretion in the antrum is thus regulated by intramural cholinergic and PACAP neurons; cholinergic neurons inhibit and PACAP neurons stimulate ANP secretion.
Gower
William R
WR
Laboratory Services, James A. Haley Veterans Administration Hospital, Tampa, Florida 33612, USA.
Dietz
John R
JR
McCuen
Robert W
RW
Fabri
Peter J
PJ
Lerner
Ethan A
EA
Schubert
Mitchell L
ML
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001285:Atropine / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D017615:Enteric Nervous System / Q000166:cytology / Q000502:physiology; D005731:Ganglionic Stimulants / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011706:Pyloric Antrum / Q000294:innervation* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C495403:Adcyap1 protein, rat; D005731:Ganglionic Stimulants; D018721:Muscarinic Agonists; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010276:Parasympatholytics; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016210:Methacholine Chloride; D004246:Dimethylphenylpiperazinium Iodide; D001285:Atropine; D009320:Atrial Natriuretic Factor