cAMP PRODUCED BY PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE 27 INHIBITS ATRIAL NATRIURETIC PEPTIDE SECRETION IN RABBIT BEATING ATRIA

SUMMARY 1 The aim of the present study was to determine the effects of increased cAMP levels in response to pituitary adenylate cyclase‐activating polypeptide 27 (PACAP27) on atrial atrial natriuretic peptide (ANP) secretion in rabbit atria. 2 A perfused beating atrial model was used in the present study and cAMP efflux and ANP levels in atrial perfusates were measured by radioimmnoassay. 3 At 100 nmol/L, PACAP27 increased cAMP production, which resulted in subsequent inhibition of ANP secretion. Nicardipine (1.0 µmol/L), an L‐type Ca2+ channel blocker, attenuated inhibition of ANP secretion by PACAP27. Staurosporine (1.0 µmol/L), a non‐specific protein kinase inhibitor, and H‐89 (1.0 µmol/L), a cAMP‐dependent protein kinase A (PKA) inhibitor, completely blocked the inhibition of ANP secretion in response to PACAP27 but had no effect on PACAP27‐induced increases in cAMP. 4 In conclusion, the results suggest that increased cAMP levels in response to PACAP27 negatively regulate ANP secretion via the adenylate cyclase–cAMP–PKA signalling pathway in rabbit atria and that L‐type Ca2+ channels may be involved, in part, in the regulation of ANP secretion by cAMP.