THE EFFECTS OF DUVERNOYS GLAND SECRETION FROM THE XENODONTINE COLUBRID PHILODRYAS-OLFERSII ON STRIATED-MUSCLE AND THE NEUROMUSCULAR-JUNCTION - PARTIAL CHARACTERIZATION OF A NEUROMUSCULAR FRACTION

The effect of Philodryas olfersii Duvernoy's secretion was studied in vivo in mice and chicks as well as in the mouse phrenic nerve-diaphrag m and the chick biventer cervicis preparations. The whole secretion (2 0-40 mu g/ml) increased the creatine kinase (CK) levels in mice but ha d no effect on the mouse phrenic nerve-diaphragm preparation, In the c hick, the secretion caused head drop and paresia as well as irreversib le blockade of the twitch-tension evoked by indirect stimulation in th e chick biventer cervicis preparation (50% paralysis in 34.5 +/- 2.7 m in, n = 4). The secretion also caused muscle contracture (30% of the m aximal twitch-tension generated) after a latency of nearly 9 min. Foll owing fractionation on a Superose 12 FPLC column, the neuromuscular ac tivity was recovered in the high mol, wt fraction (Peak I). At a conce ntration of 10 mu g/ml in the chick biventer cervicis preparation, Pea k I caused 50% paralysis within 18.5 +/- 3.0 min (n = 4), and evoked a strong contracture (70%, of the maximal twitch-tension generated). Th e contractile responses of the chick preparation to ACh and KCl were p artially blocked (90%) by the whole secretion and totally blocked by P eak I. CK release was increased by the whole secretion but not by Peak I. The whole secretion also produced various degrees of muscle cell l ysis and extensive widening of the intercellular spaces. The latter sh owed a loosely arranged membranous network. In general, Peak I caused only minor morphological alterations compared with the whole secretion , although these were still significantly different from those observe d in the control preparations. The changes principally involved hyperc ontraction of the muscle fibers. Based on the above results, we conclu de that Peak I contains the factor(s) responsible for the in vitro eff ects on neuromuscular transmission, whereas the direct myotoxic effect is apparently caused by at least one other component of the Duvernoy' s secretion. (C) 1996 Elsevier Science Ltd.