Regulation of atrial natriuretic peptide (ANP) secretion
To investigate the role of calcium, protein kinase C and adenylate cyclase in the ANP secretion, the secretory responses from isolated perfused rat hearts to a calcium channel activator, Bay k8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluomethylphenyl)-2-pyridine-5-carboxylate), the calcium ionophore (A23187), the phorbol ester (12-0-tetradecanoylphorbol-13-acetate, TPA), and to forskolin were studied. ANP in perfusate was measured by radioimmunoassay 10 min before and during the infusion (30 min) of various agents at 2 min intervals. A23187 (5.7 x 10/sup -7/) induced a sharp increase, whereas TPA (0.15 - 1.6 x 10/sup -7/) caused a slowly progressive increase in ANP secretion. 4a-phorbol-12,13-didecanoate, a non-active phorbol ester, had no effect on ANP secretion. Bay k8644 (4 x 10/sup -7/) and forskolin (1 x 10/sup -6/) alone caused small but sustained increase in ANP secretion. The combination of TPA with Bay k8644, forskolin or A23187 stimulated ANP secretion higher than the calculated additive value for each agent. Dibuturyl-cAMP (1.6 x 10/sup -4/) pretreatment also enhanced TPA-induced ANP release. 8-Bromo-cGMP (1.3 x 10/sup -4/) and sodium nitroprusside (9 x 10/sup -5/) alone had no effect, but both attenuated the TPA-induced ANP secretion. The results suggest that atrial cardiocytes possess at least two different secretory pathways for ANP secretion, which are probably dependent on protein kinase C and cyclic AMP.
- Research Organization:
- Univ. of Heidelberg, West Germany
- OSTI ID:
- 6774528
- Report Number(s):
- CONF-8604222-; TRN: 87-009083
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
PEPTIDES
SECRETION
PHORBOL ESTERS
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
CYCLASES
MAPS
PERFUSED ORGANS
PHOSPHOTRANSFERASES
RADIOIMMUNOASSAY
RATS
ANIMALS
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CARCINOGENS
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ORGANS
PHOSPHORUS-GROUP TRANSFERASES
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