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Pharmacology identification of two related pentapeptides from the brain with potent opiate agonist activity
329 tion of the ipsilateral canine tooth pulp and not the contralateral one. Most were also excited by tactile stimulation of the surrounding trigeminal field. Latencies to tooth pulp stimulation ranged from 5.1 to 22.8 msec. All were located at or just below the border of the magnocellular layer of trigeminal nucleus caudalis, Another group of neurons was excited by bilateral canine stimulation. Late&es ranged from 7 to 28 msec. All were also excited by ipsilateral cornea1 mechanical stimulation and firm pressure applied to the face bilaterally. All were located deep to nucleus caudalis in a reticular area continuous with nucleus gigantocellularis of the reticular formation. It is concluded that the first class of unit is functionally similar to spinal cord dorsal horn lamina V neurons, while the second class may be the trigeminal contribution to medial spinoreticular pathways.
PHARMACOLOGY Identification of two opiate agonist activity
related
pentapeptides
from
the brain
J. Hughes, T.W. Smith, H.W. Kosterlitz, L.A. Fothergill, H.R. Morris, Nature (Lond.), 258 (1975) 577-579
with potent
B.A. Morgan and
The existence of an endogenous substance in the brain which acts as an agonist at opiate receptor sites has been repeatedly confirmed. In the present paper this substance, termed enkephalin, was shown to be composed by two pentapeptides which have been identified and synthesised, Enkephalin was isolated from pig brains. Following investigations by sequential degradation and by mass spe~tromet~y, enkephalin was interpreted as being the result of a mixture of the two pentapeptides H-Tyr-Gly-Gly-PheMet-OH (methionine enkephalin) and H-Tyr-Gly-Gly-Phe-Leu-OH (leucine enkephalin). The ratio between the two peptides appears to be 3 or 4 to 1. Both methionine and leucine enkephalins have potent agonist activity at opiate receptors sites in that they produce a dose-related inhibition of electrically evoked contractions of the mouse vas deferens and the guinea pig ileum. These inhibitor effects could be completely ~~gonized by naloxone. Preliminary results on the inhibitory effects of methionine enkephalin on the stereospecific binding of [3H]naloxone in Na’ free homogenates of guinea pig brain indicate that methionine enkephalin is at least three times more potent than morphine. It is particularly interesting that the methionine enkephalin sequence is present as residue 61-65 in beta-lipotropin isolated from pituitary glands of,sheep, pig and man. Beta-lipotropin may be a common precursors for ACTH, MSH and methionine enkephalin. The authors are now planning to test the hypothesis that enkeph~ins act as neurotransmitters or neuromodulator at synaptic junction.
PHARMACOLOGY Identification of two opiate agonist activity
related
pentapeptides
from
the brain
J. Hughes, T.W. Smith, H.W. Kosterlitz, L.A. Fothergill, H.R. Morris, Nature (Lond.), 258 (1975) 577-579
with potent
B.A. Morgan and
The existence of an endogenous substance in the brain which acts as an agonist at opiate receptor sites has been repeatedly confirmed. In the present paper this substance, termed enkephalin, was shown to be composed by two pentapeptides which have been identified and synthesised, Enkephalin was isolated from pig brains. Following investigations by sequential degradation and by mass spe~tromet~y, enkephalin was interpreted as being the result of a mixture of the two pentapeptides H-Tyr-Gly-Gly-PheMet-OH (methionine enkephalin) and H-Tyr-Gly-Gly-Phe-Leu-OH (leucine enkephalin). The ratio between the two peptides appears to be 3 or 4 to 1. Both methionine and leucine enkephalins have potent agonist activity at opiate receptors sites in that they produce a dose-related inhibition of electrically evoked contractions of the mouse vas deferens and the guinea pig ileum. These inhibitor effects could be completely ~~gonized by naloxone. Preliminary results on the inhibitory effects of methionine enkephalin on the stereospecific binding of [3H]naloxone in Na’ free homogenates of guinea pig brain indicate that methionine enkephalin is at least three times more potent than morphine. It is particularly interesting that the methionine enkephalin sequence is present as residue 61-65 in beta-lipotropin isolated from pituitary glands of,sheep, pig and man. Beta-lipotropin may be a common precursors for ACTH, MSH and methionine enkephalin. The authors are now planning to test the hypothesis that enkeph~ins act as neurotransmitters or neuromodulator at synaptic junction.