Effect of alterations in the cyclopentane ring on bone resorptive activity of prostaglandin

Journal Article · Wed Feb 01 04:00:00 EST 1989 · Prostaglandins; (United States)

DOI:https://doi.org/10.1016/0090-6980(89)90059-2· OSTI ID:5934414

Raisz, L G; Woodiel, F N

Previous studies have shown that the natural prostanoids, PGE2, PGE1 and PGF2 alpha are potent stimulators of bone resorption. In this study, we have examined the effects of alterations in the cyclopentane ring of these prostanoids for their effect on the resorptive response of cultured long bones from 19-day fetal rats as measured by the release of previously incorporated /sup 45/Ca. Indomethacin (10(-6)M) was added to minimize endogenous prostaglandin production. In this system PGE2 and PGE1, the 9 keto, 11 alpha hydroxy compounds, were approximately equally effective at concentrations of 10(-8) to 10(-6) M. The 9 alpha hydroxy, 11 alpha hydroxy compound, PGF2 alpha, was active at 10(-7) to 10(-5) M. In contrast, the 9 alpha hydroxy, 11-keto compound, PGD2, showed only a minimal stimulation of bone resorption at 10(-5) M. While these data suggested that the 11 alpha hydroxy group was important for bone resorbing activity, 11 beta PGE2 and 11-deoxy PGE1 were only slightly less potent than their physiologic counterparts. Both 9 beta, 11 alpha PGF2 and 9 alpha, 11 beta PGF2 were less potent than PGF2 alpha but did cause substantial stimulation of bone resorption and were equally effective at 10(-6) to 10(-5) M. 9 alpha, 11 beta PGF2 alpha is of particular interest since it is major metabolite of PGD2. These results suggest that the binding of prostanoids to the receptor which mediates bone resorption is affected by changes at the 9 and 11 positions of the pentane ring but do not support the hypothesis that the 11 alpha OH function is essential for this biological activity.

• Research Organization: Univ. of Connecticut Health Center, Farmington (USA)
• OSTI ID: 5934414
• Journal Information: Prostaglandins; (United States), Journal Name: Prostaglandins; (United States) Vol. 37:2; ISSN PRGLB
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CALCIUM 45
CALCIUM ISOTOPES
DAYS LIVING RADIOISOTOPES
EVEN-ODD NUCLEI
FETUSES
IN VITRO
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROSTAGLANDINS
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SKELETON
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
VERTEBRATES