The serum of a non-venomous striated snake, Elaphe quadrivirgata, was found to contain phospholipase A2 (PLA2) inhibitory proteins (PLIs). One of these inhibitors was purified by Sephadex G-200 gel filtration, Q-Sepharose FF ion-exchange chromatography and Butyl Sepharose 4FF hydrophobic chromatography. The purified PLI inhibited the enzymic activities of all PLA2 groups, including Elapidae venom (group-I), Viperidae venom (group-II) and honeybee PLA2s (group-III). The inhibitor was a 130 kDa glycoprotein consisting of two distinct subunits, A and B, of 30 and 29 kDa respectively; each of which was glycosylated with N-linked oligosaccharide chains. The cDNAs encoding the respective inhibitor subunits were isolated from a liver cDNA library by the use of probes, prepared by PCR, based on the partially determined amino-acid sequences of the corresponding subunits. The respective nucleotide sequences encoded 19-amino-acid-residue signal sequences, followed by 183- and 181-residue protein sequences for the A and B subunits respectively. The amino-acid sequences revealed that the E. quadrivirgata inhibitor corresponded to PLIgamma, one of three kinds of inhibitors purified from venomous snakes. The existence of PLIgamma in the serum of this non-venomous snake suggested that, besides having a protective role against the venom PLA2s of other venomous snakes, PLIgamma has other important physiological functions in regulating local PLA2 activities; and thus it raises the possibility that PLIgamma occurs in other animals, including mammals.

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Abstract:To investigate the association between streptozotocin (STZ)-induced painful diabetic neuropathy and the antihyperalgesic effect of capsaicin cream in rats, we first examined the antihyperalgesic effect of capsaicin cream and subsequently performed peripheral neurohistochemical examinations of neuropathic rats. Mechanical hyperalgesia occurred 2 weeks after STZ injection and persisted for 8 weeks of testing. The neuropathy was alleviated by a single application of 0.1% capsaicin cream, but not by cream base. The hyperalgesia did not decrease when the capsaicin cream was applied to normal animals. On the other hand, for dorsal root ganglion (DRG) neurons and hind paw cutaneous nerves, the neurohistochemical examination showed no difference between STZ rats and control rats with capsaicin (vanilloid) receptor subtype 1 (VR1) and NF200 double immunohistochemical staining of DRG neurons, but an increase in A-fibers was seen in the hind paw cutaneous nerves of the STZ rats compared to the control rats. Neither STZ rats nor control rats were toxically affected by the single application of 0.1% capsaicin cream. These results suggest that a single application of capsaicin cream exerts an antihyperalgesic effect in rats with painful neuropathy and increases peripheral A-fibers. However, we could not clarify how VR1 was involved in the effect in rats with STZ painful diabetic neuropathy. (J Toxicol Pathol 2008; 21: 97-104)

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