A novel multifunctional metabolic pathway in a marine mollusc leads to unprecedented prostaglandin derivatives (prostaglandin 1,15-lactones)

Abstract

The discovery of high levels of prostaglandin (PG) 1,15-lactones of both the E and F series and their co-existence with PGs has been recently described in the opisthobranch mollusc Tethys fimbria. The present study was undertaken in order to investigate the biosynthesis of these novel natural PG derivatives in vivo using radiolabelled precursors, and to gain a preliminary understanding of their biological role. PGE2 1,15-lactone was shown to be produced from both PGE2 and PGF2 alpha in the mollusc mantle and appeared to be quickly transferred to the mollusc dorsal appendices (cerata). The detachment of the latter during the typical defence behaviour of T. fimbria was accompanied by the conversion of PGE2 and PGE3 1,15-lactones back to the corresponding PGs. Both PGE2 and PGE2 1,15-lactone were also shown to be biosynthesized from arachidonic acid. Lactones of the F series were present as 11-acetyl derivatives in T. fimbria mantle and as 9- and 11-fatty acyl esters in the mollusc egg-mass and reproductive gland, and their biosynthesis from PGF2 alpha was demonstrated in all of these tissues. A multiple biological role of PG 1,15-lactones in T. fimbria defensive behaviour, smooth muscle contraction and egg production/fertilization control is hypothesized. The high amounts of PG derivatives found in T. fimbria and the biosynthetic studies described herein indicate that this marine mollusc may be a useful model for future studies on PG biosynthesis.

Factors promoting marine invasions: A chemoecological approach

“…In T. fimbria, it was suggested that prostaglandin E 2 -1,15-lactone 4 acts as chemical mediator in the defense (26). It was also shown that it has a de novo origin from arachidonic acid (36). In the case of the Lessepsian M. viridis, the ichthyotoxic compound 4 was not detected in the extract obtained from the animal bodies, which include the digestive apparatus, also supporting a nondietary origin of this metabolite, whereas its presence both in the cerata and in the slime released by the mollusk during autotomy suggested its involvement in chemical defense.…”

Prostaglandins in non-insectan invertebrates: recent insights and unsolved problems

“…One of the most impressive series of studies on PG biosynthesis in invertebrates comes from the work on the opistobranch mollusc, Tethrys fimbria (Cimino et al, 1989(Cimino et al, , 1991aDi Marzo et al, 1991). These authors showed conclusively that this mollusc generates novel PG derivatives, the PG 1,15-lactones, apparently derived from PGE 2 and PGF 2α .…”

“…These authors showed conclusively that this mollusc generates novel PG derivatives, the PG 1,15-lactones, apparently derived from PGE 2 and PGF 2α . The product profile in T. fimbriae also differs between the mantle, cerata and reproductive glands (Cimino et al, 1991b;Di Marzo et al, 1991), with PGs formed in the mantle exported to the cerata and reproductive glands where further structural modification occurs. This regional-specific generation of PGs may imply that these products perform different functions such as defence in the cerata, and control of the reproductive processes in the ovary/testis (Di Marzo et al, 1991).…”

“…The product profile in T. fimbriae also differs between the mantle, cerata and reproductive glands (Cimino et al, 1991b;Di Marzo et al, 1991), with PGs formed in the mantle exported to the cerata and reproductive glands where further structural modification occurs. This regional-specific generation of PGs may imply that these products perform different functions such as defence in the cerata, and control of the reproductive processes in the ovary/testis (Di Marzo et al, 1991). Because these studies have fully characterised the products formed and their mode of biosynthesis, T. fimbria would make a good model for detailed investigations aimed to determine the functional significance and mechanism of action of the PGs formed.…”

The identification and role of a novel eicosanoid in the reproductive behaviour of barnacles (Balanus balanus)

“…Furthermore, many marine invertebrates, such as corals, ascidians, bryozoans and barnacles, have been found to biosynthesize both 'classical' eicosanoids (i.e. those found in mammals) and novel forms including clavulones, mucosin, prostaglandin 1,15-lactones, and bromo-and iodo-vulones from these alternate fatty acid substrates (DiMarzo et al, 1991;Casapullo et al, 1997;Rowley et al, 2005). With a few notable exceptions (e.g.…”