Prostaglandin E1 Is an Efficient Molecular Tool for Forest Leech Blood Sucking

Abstract

From a survival perspective, it is hypothesized that leech saliva exhibits certain physiological effects to ensure fast blood-feeding, including analgesia, anesthesia, and anti-inflammation to stay undetected by the host and vasodilatation and anti-hemostasis to ensure a steady, rapid, and sustained blood flow to the feeding site. Many anti-hemostatic compounds have been identified in leech saliva, such as hirudin, calin, and bdellin A. However, no specific substance with direct vasodilatory and anti-inflammatory function has been reported from forest leech saliva. Herein, using activity-guided analysis, prostaglandin E1 (PGE1) was identified for the first time as an efficient molecular tool for forest leech blood sucking. The structure of PGE1 was analyzed by nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectroscopy. PGE1 was found to be primarily distributed in the leech salivary gland (1228.36 ng/g body weight). We also analyzed how forest leech PGE1 affects platelet aggregation, skin vascular permeability, bleeding time, and pain. Results indicated that PGE1 efficiently inhibited platelet aggregation induced by adenosine diphosphate (ADP) (5 μM) with an IC50 of 21.81 ± 2.24 nM. At doses of 10, 100 nM, and 1 μM, PGE1 increased vascular permeability by 1.18, 5.8, and 9.2 times. It also prolonged bleeding time in a concentration-independent manner. In the formalin-induced mouse paw pain model, PGE1 suppressed acute pain. To the best of our knowledge, this is the first report on PGE1 in invertebrates. The functions of PGE1, such as vasodilation, platelet aggregation inhibition, anti-inflammation, and pain alleviation, may facilitate the ingestion of host blood by leeches.

The Role of Prostaglandin E1 as a Pain Mediator through Facilitation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 via the EP2 Receptor in Trigeminal Ganglion Neurons of Mice

“…In this study, the ED 50 of the I h facilitation effect by PGE1 was ~30 nM, and the concentration mainly used in this experiment was 100 nM. Consistent with previous studies, these concentration ranges are physiologically active in vivo and similar to the concentration ranges of antithrombotic action [33,34]. Moreover, the production of PGE1, which exhibits ~20 times stronger biological properties than PGE2 [4], can be determined according to the COX activity or the DGLA/AA ratio [1,35].…”

“…A recent study reported that the EP4 receptor mediates PGE2-induced excitation via HCN2 channels by activating adenylate cyclase [14]. Other studies have suggested that the EP2 receptor subtype mediated spinal inflammatory hyperalgesia by facilitating HCN2 channels [33,34]. An EP2 blocker, AH6809, inhibited PGE1-induced facilitation of I h and PGE1-induced orofacial pain, but neither an EP1 blocker nor an EP4 blocker had the same effect.…”

How do Vampires Suck Blood?

“…It has been also reported that PGE2 could inhibit wound healing by recruiting fibroblasts to the feeding lesion 27 . In addition to PGE2, PGF2 alpha was also commonly detected in bloodsuckers with reported functions of vasodilation, platelet aggregation inhibition, anti-inflammation, and pain alleviation 25, 31 . In this study, we have detected another two PGs, i.e., PGJ2 and PGE3, in lamprey buccal gland.…”

“…Prostaglandins (PGs) are eicosanoid components derived from arachidonic acid through three sequential enzymatic reactions. They act as 'local hormones' and regulate a plethora of physiological processes 31,48 . PGs are a group of well-studied blood-sucking related metabolites, and they have been discovered in many bloodsuckers, including ticks [25][26][27][28] , salmon louses 29,30 and forest leeches 31 .…”

“…3e). PGs are a group of well-studied blood-sucking related metabolites with vasodilatory and immunomodulatory capabilities, and they have been discovered in the saliva of many bloodsuckers such as tick [25][26][27][28] , salmon louse 29,30 and forest leech 31 . It is well established that there is great similarity in the salivary components among different bloodsuckers, and one consistency is the presence of PGs.…”