Regulation of cyclic AMP metabolism by prostaglandins in rabbit cortical collecting tubule cells

Thesis/Dissertation · Thu Jan 01 00:00:00 EST 1987

OSTI ID:6280630

Sonnenburg, W K

In the rabbit cortical collecting tubule (RCCT), prostaglandin E/sub 1/ (PGE/sub 1/) and prostaglandin E/sub 2/ (PGE/sub 2/) at 1 nM inhibit arginine-vasopressin (AVP)-induced water reabsorption, while 100 nM PGE/sub 1/ and PGE/sub 2/ alone stimulate water reabsorption. Reported here are studies designed to investigate the molecular basis for the biphasic physiological action of PGE/sub 1/ and PGE/sub 2/ in the collecting duct. In freshly isolated RCCT cells, PGE/sub 1/, PGE/sub 2/, and 16,16-dimethyl-PGE/sub 2/ (DM-PGE/sub 2/) stimulated cAMP synthesis at concentrations ranging from 0.1 to 10 M. Other prostaglandins including the synthetic PGE/sub 2/ analogue, sulprostone, failed to stimulate cAMP synthesis. Moreover, sulprostone did not antagonize PGE/sub 2/-stimulated cAMP formation. In contrast, PGE/sub 2/ and sulprostone at concentrations ranging from 1 to 100 nM, inhibited AVP-induced cAMP accumulation in freshly isolated RCCT cells. PGE/sub 2/, PGE/sub 1/, DM-PGE/sub 2/ and sulprostone at 100 nM were equally effective in inhibiting AVP-induced cAMP formation. Moreover sulprostone inhibited AVP-stimulated adenylate cyclase activity. These results suggest that PGE derivatives mediate either inhibition or activation of adenylate cyclase by stimulating different PGE receptors. To further test this concept, PGE/sub 2/ binding to freshly isolated RCCT cell membranes was characterized. Two different classes of PGE/sub 2/ binding were detected. //sup 3/H/PGE/sub 2/ binding to the high affinity class of sites was increased by the GTP-analogue, GTP S, while pertussis toxin pretreatment blocked the stimulatory action. In contrast, //sup 3/H/ PGE/sub 2/ binding to the low affinity class of sites was decreased by GTP S; this inhibitory effect was not blocked by pertussis toxin pretreatment.

• Research Organization: Michigan State Univ., East Lansing (USA)
• OSTI ID: 6280630
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMP
METABOLISM
PROSTAGLANDINS
BIOCHEMICAL REACTION KINETICS
CELL MEMBRANES
CYCLASES
RABBITS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUBULES
ANIMALS
BODY
CELL CONSTITUENTS
ENZYMES
ISOTOPE APPLICATIONS
KIDNEYS
KINETICS
LABELLED COMPOUNDS
LYASES
MAMMALS
MEMBRANES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
REACTION KINETICS
VERTEBRATES
550501* - Metabolism- Tracer Techniques