Opiate-like Activity Research Articles

The possible role of enkephalin in the mechanism of acupuncture analgesia in man

On the basis of recent research on the presence and function of an endogenous peptide with opiate-like activity present in the brain, and the developing understanding of the physiological mechanism of acupuncture analgesia, it is postulated that the analgesic effects of acupuncture are mediated through the action of this substance on the neural mechanism(s) of pain inhibition.

Characterization of the endorphins, novel hypothalamic and neurohypophysial peptides with opiate-like activity: evidence that they induce profound behavioral changes

(1) α-, β-, γ-endorphins have primary structures respectively identical to those of β-lipotropin subunits [61–76], [61–91], [61–77]. (2) These peptides exhibit opiate-like activity in several assay systems. (3) A series of analogs of the naturally occurring peptides has been prepared and their biologic activities compared. (4) Each of the endorphins produces a discrete set of profound behavioral changes when injected into the ventricular system of the brain of rats. (5) The hypothesis is advanced that alterations in the homeostasis of the β-lipotropinendorphin system may be causally involved in the mental diseases of man.

Opioid properties of β-lipotropin fragment 60–65, HArgTryGlyGlyPheMetOH

The pharmacologic activity of the hexapeptide fragment corresponding to the amino acid fragment 60–65 in β-lipotropin, (β-LPH-(60–65)) was studied in vitro and in vivo . In binding assays on synaptosomal plasma membrane the peptide was found to be equipotent to met-enkephalin, but behaved differently to cations; in contrast to met-enkephalin both Mn +2 and Na + enhanced the binding of β-LPH-(60–65) to synaptosomal plasma membrane. On both the quinea pig ileum and mouse vas deferens β-LPH-(60–65) inhibited contractions elicited by electrical stimulation and each effect was reversible by naloxone. On the guinea pig ileum β-LPH-(60–65) was equipotent to met-enkephalin and 0.5 as potent as normorphine but on the vas deferens it was 4.6 times more potent than normorphine. The activities of β-LPH-(60–65) appear to be due to the intact compound rather than to its conversion to met-enkephalin, since the peptide extracted from the ileum assay was found to behave identically as β-LPH-(60–65) with high pressure liquid chromatography. When β-LPH-(60–65) was administered centrally to mice and rats, no overt central actions were observed and an antinociceptive effect could not be demonstrated. Nor did β-LPH-(60–65) antagonize morphine action or precipitate the withdrawal syndrome in morphine dependent animals. It is concluded that the good agreement which generally exists between in vitro and in vivo assay procedures for opiate-like activity of morphine and its surrogates does not necessarily hold for the endogenous peptides with similar actions.

β-Endorphin in vitro inhibition of striatal dopamine release

THERE has been considerable recent interest in endogenous peptides as possible analgesic agents since the isolation of a pentapeptide with opiate-like activity (methionine-enkephalin) from porcine brain1. Of particular interest is β-endorphin, isolated from camel pituitary glands2, and now synthesised3. We report here the inhibitory effect in vitro of β-endorphin on striatal dopamine release from the central nervous system (CNS).

Porcine pituitary peptides with opiate-like activity: partial purification and effects in the rat after intraventricular injection.

A peptide material with opiate-like activity in the guinea-pig ileum was extracted from porcine pituitaries using a hot glacial acetic acid extraction method and was partially purified by gel filtration. When injected intraventricularly in rats, these purified peptides induced strong analgesia, catelepsy, respiratory depression and other opiate-like effects, which lasted for several hours.

Tolerance and dependence induced by morphine-like pituitary peptides in rats

An extract from porcine pituitaries containing peptides with opiate-like activity (endorphins) was investigated for possible tolerance/dependence liability in rats. Repeated intraventricular administration of endorphins induced a degree of tolerance similar to that induced by normorphine. Rats made tolerant to morphine by repeated pellet implantation proved cross-tolerant to the pituitary extract as well as to synthetic methionine-enkephalin. Naloxone given to rats, repeatedly pretreated with endorphins, precipitated a withdrawal syndrome strongly resembling that induced in rats treated with normorphine. Withdrawal precipitated in morphine-dependent rats was suppressed by intraventricularly applied endorphins. The results suggest that identical sites and mechanisms are involved in the development of tolerance/dependence induced by opiates and pituitary endorphins.

Beta-endorphin is a potent analgesic agent.

beta-Endorphin, an opiate-like peptide, has potent antinociceptive properties when it is administered directly into the brain and assayed in the the tail-flick, hot-plate, and writhing tests in mice and in the wet shake test in rats. On a molar basis, beta-endorphin is 18 to 33 times more potent than morphine and its actions are blocked by the specific opiate antagonist, naloxone hydrochloride. The activity of beta-endorphin in vivo is also compared to other peptides that show opiate-like activity in assays in vitro.