Regulation of cAMP metabolism by PGE2 in cortical and medullary thick ascending limb of Henle's loop.
We have examined the regulation by prostaglandin E2 (PGE2) of hormone-induced adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in cells isolated by immunodissection from both the medullary and cortical thick ascending limb of Henle's loop of rabbit kidney. At concentrations greater than 10(-8) M, PGE2, but not sulprostone (16-phenoxy-17,18,19,20-tetranor-PGE2 methylsulfonilamide), caused cAMP accumulation in both cortical and medullary thick limb cells. However, at concentrations of less than or equal to 10(-8) M, both PGE2 and sulprostone inhibited arginine vasopressin (AVP)-, calcitonin-, and glucagon-induced cAMP accumulation in medullary thick ascending limb (mTAL) cells. In cortical thick limb (cTAL) cells, sulprostone also inhibited AVP-, calcitonin-, and parathyroid hormone (PTH)-induced cAMP accumulation. The inhibitory effects of PGE2 and of sulprostone were blocked by pretreatment of mTAL and cTAL cells with pertussis toxin. Membranes prepared from mTAL cells exhibited a [3H]PGE2 binding activity that was stimulated on addition of the stable guanosine 5'-triphosphate (GTP) analogue, 5'-guanosine gamma-thiotriphosphate (GTP gamma S); moreover, sulprostone inhibited [3H]PGE2 binding. Our results suggest that PGE2 can function via a prostaglandin E receptor linked to a guanine nucleotide regulatory protein, Gi, to attenuate hormone-induced cAMP formation in both mTAL and cTAL cells of rabbit kidney.
Nakao
A
A
Department of Biochemistry, Michigan State University, East Lansing 48824.
Allen
M L
ML
Sonnenburg
W K
WK
Smith
W L
WL
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D007700:Kinetics; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D037342:Pertussis Toxin; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000378:metabolism; D019379:Teriparatide; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011982:Receptors, Prostaglandin; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D019379:Teriparatide; D001127:Arginine Vasopressin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C016767:sulprostone; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D015232:Dinoprostone