Peptides. Vol. 7, pp. 551-556, 1986. ©Ankho InternationalInc. Printed in the U.S.A. 0196-9781/86 $3.00 + .00 Met-Enkephalin-Induced Release Into the Blood of a Factor Causing Postural Asymmetry G. Ya. BAKALKIN, 1 A. G. KOBYLYANSKY, L. V. NAGORNAYA, K. N. YARYGIN AND M. I. TITOV USSR Cardiology Research Center, Academy of Medical Sciences, Moscow Received 8 February 1985 ~BAKALKIN, G. Ya., A. G. KOBYLYANSKY, L. V. NAGORNAYA, K. N. YARYGIN AND M. I. TITOV. Met- enkephalin-induced release into the blood of a factor causing postural asymmetry. PEPTIDES 7(4) 551-556, 1986.--Met- and Leu-enkephalin applied subarachnoidally into the rostral portion ofa transected spinal cord (at the T6--T7 level) induce postural asymmetry of the hind limbs in rats, Met-enkephalin being predominantly responsible for the flexion of the right, and Leu-enkephalin of the left, hind leg. The blood serum of rats injected with Met-enkephalin contains a factor which, when administered subarachnoidally into the caudal portion of the transected spinal cord, is capable of inducing the hind limb postural asymmetry--predominantly, with the right leg flexion. This factor is inactivated by papain and differs from Met- and Leu-enkephalin in chromatographic properties. Apparently, Met-enkephalin induces the release of a peptide factor into the blood, from the brain or organs innervated by the neurons lying above the cut. It is then carried with the blood to the hind limbs and effects the hind limb postural asymmetry. Enkephalins Hind limb postural asymmetry Left/fight flexion ratio WE have recently found that enkephalins injected into sub- arachnoidal space of the caudal portion of transected spinal cord induce postural asymmetry of the hind legs [4]. Leu- enkephalin predominantly causes flexion of the right hind limb, and Met-enkephalin of the left one. These data indicate that the neurons, located symmetrically to the sagittal plane, which maintain muscular tone of the hind limbs, have differ- ent sensitivity to enkephalins. In most animals, the neurons with a higher specificity to some enkephalin are localized on the one side of the sagittal plane. An opiate antagonist, naloxone, prevents enkephalin ef- fects which suggests that opiate receptors are involved in the development of postural asymmetry. Since the side of the flexed limb depends on the type of injected enkephalin, the action of Leu- and Met-enkephalin is likely mediated by dif- ferent opiate receptors. Lateral asymmetry of these recep- tors in the spinal cord apparently underlies the development of postural asymmetry. Opiate receptors are widely distributed in the brain and spinal cord. Generally, higher opiate receptor densities in the spinal cord were found in the grey matter as compared with the white matter. A high receptor density was seen in the dorsal horn and specifically in the dorsal layer of the sub- stantia gelatinosa [1, 2, 9, 19]. These receptors may be in- volved in the regulation of spinal motor reflexes. Indeed, morphine and other opioids alter electrical activity of spinal moto- and interneurons [5, 8, 12, 18], as well as flexor reflex in intact and spinal animals [5,14]. The present study showed that enkephalins administered into the rostral portion of a transected spinal cord also in- duce postural asymmetry of the hind limbs in rats. This phe- nomenon may be accounted for by the newly revealed prop- erty of enkephalins, i.e., their capability to release some factor from the brain into the blood which selectively affect the neurons lying to the left or to the right of the central sagittal plane. METHOD Male Wistar rats weighing 150 to 180 g obtained from the "Stolbovaya" nursery of the USSR Academy of Medical Sciences were used in experiments. Animals were housed in an environmentally controlled room having a 14:l0 day:night (lights on at 8.00 and offat 22.00 hr). Rats were operated on from 10 a.m. till 2 p.m. under ether anesthesia. The spinal cord was doubly ligated at T5-T8 and the studied substances dissolved in saline were administered intravenously (0.3 ml/animal) or subarachnoidally (10 /zl/animal). The latter procedure was performed using a stainless steel or polyeth- ylene catheter (0.4 mm external diameter). The catheter was inserted under the dura mater 3 mm caudally or rostrally to the lower or upper ligature respectively and fixed, and the 1Requests for reprints should be addressed to Dr. G. Ya. Bakalkin, USSR Research Center of Cardiology, 3rd Cherepkovskaya str., 15A, Moscow 121552. 551