Reciprocal paracrine pathways link atrial natriuretic peptide and somatostatin secretion in the antrum of the stomach.
Atrial natriuretic peptide (ANP) as well as its receptor, NPR-A, have been identified in gastric antral mucosa, suggesting that ANP may act in a paracrine fashion to regulate gastric secretion. In the present study, we have superfused antral mucosal segments obtained from rat stomach to examine the paracrine pathways linking ANP and somatostatin secretion in this region.ANP (0.1 pM to 0.1 microM) caused a concentration-dependent increase in somatostatin secretion (EC(50), 0.3 nM). The somatostatin response to ANP was unaffected by the axonal blocker tetrodotoxin but abolished by addition of the selective NPR-A antagonist, anantin. Anantin alone inhibited somatostatin secretion by 18+/-3% (P<0.005), implying that endogenous ANP, acting via the NPR-A receptor, stimulates somatostatin secretion. Somatostatin (1 pM to 1 microM) caused a concentration-dependent decrease in ANP secretion (EC(50), 0.7 nM) that was abolished by addition of the somatostatin subtype 2 receptor (sst2) antagonist, PRL2903. Neutralization of ambient somatostatin with somatostatin antibody (final dilution 1:200) increased basal ANP secretion by 70+/-8% (P<001), implying that endogenous somatostatin inhibits ANP secretion. We conclude that antral ANP and somatostatin secretion are linked by paracrine feedback pathways: endogenous ANP, acting via the NPR-A receptor, stimulates somatostatin secretion, and endogenous somatostatin, acting via the sst2 receptor, inhibits ANP secretion.
Gower
W R
WR
Department of Medicine, University of South Florida and James A. Haley Veterans Hospital, Tampa, FL, USA.
McCuen
R W
RW
Arimura
A
A
Coy
D A
DA
Dietz
J R
JR
Landon
C S
CS
Schubert
M L
ML
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D019899:Paracrine Communication / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013004:Somatostatin / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
D000906:Antibodies; C121568:PRL 2903; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C476020:atrial natriuretic factor (4-23); C106140:somatostatin receptor sst2A; C068090:anantin; D013004:Somatostatin; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C