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Biomedical subjects

L Terenius

Publications and source records attributed to L Terenius.

At least 361 records · Page 20Linked to original sources

Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: enkephalin and substance P.

The distribution of Met-enkephalin- and substance P-immunoreactive neurons was studied by indirect immunofluorescence in some areas related to pain and analgesia. Met-enkephalin- and substance P-positive cell bodies and nerve terminals were observed in the periaqueductal central gray, the nucleus raphe magnus, the marginal layers and substantia gelatinosa of the spinal trigeminal nucleus, and the dorsal horn of the spinal cord. Lesion experiments suggest that Met-enkephalin neurons in the dorsal horn and possibly in the spinal trigeminal nucleus are interneurons or propriospinal neurons with nerve terminals in the laminae I and II of the cord and in the superficial layers of the spinal trigeminal nucleus, respectively. These areas are also very rich in substance P-positive nerve terminals, mainly representing central branches of primary afferent neurons. The present immunohistochemical-anatomical findings support the hypothesis that stimulation-produced analgesia is related to activation of spinal and spinal trigeminal enkephalin interneurons forming axo-axonic synapses with (substance P?) pain afferents in the superficial laminae of the dorsal horn and the spinal trigeminal nucleus. These interneurons may be activated by sensory fibers and by descending fibers from medullary stimulation sites. Transmitter substances in these descending fibers may be 5-hydroxytryptamine and substance P.

Analgesia↗

A method for site selectivity analysis applied to opiate receptors.

A method has been developed to determine whether or not a receptor system consists of several sites with different binding specificity. Several radioactive indicator drugs are used in solutions of identical chemical composition. Homogeneity of the receptor system is tested graphically. We have applied the method to a study of opiate receptors. It appeared that there were at least two different binding sites. Several different competitors with various characteristics have been tested against three indicator solutions with radioactive dihydromorphine, naloxone and naltrexone respectively. Three different classes of opiates were observed in the system, morphine-like, naltrexone-like and an intermediate group. A morphine-like substance shows high selectivity for one of the sites while naltrexone-like compounds show practically no discrimination between the sites and a group of partial agonists such as nalorphine is intermediate.

Animals↗

Interaction between ACTH fragments, brain opiate receptors and morphine-induced analgesia.

The present study confirms that N-terminal fragments of ACTH have an affinity for rat brain opiate receptors in vitro. Such peptides, devoid of corticotrophic activity, were found to inhibit morphine-induced analgesia if they also possessed affinity for opiate receptors in vitro. The structure-activity relationship for these two parameters is comparable to that observed for the same peptides on the induction of excessive grooming.

Adrenocorticotropic Hormone↗

Somatostatin and ACTH are peptides with partial antagonist-like selectivity for opiate receptors.

The peptides, Met-enkephalin and somatostatin were analysed for competitive affinity to opiate agonist receptor sites in rat brain. Met-enkephalin, like morphinomimetic compounds, being equal to marked selectivity for agonist sites while somatostatin and ACTH showed much less selectivity, being equal to partial antagonists like nalorphine. These results are compared with those observed for these peptides in vivo. It is suggested that somatostatin and acth act as partial agonist--antagonist on opiate receptors in the cns.

Adrenocorticotropic Hormone↗

Immunohistochemical studies using antibodies to leucine-enkephalin: initial observations on the nervous system of the rat.

Enkephalins are peptides which have pharmacological properties similar to those of morphine. Guinea pigs were immunized with a leucine-enkephalin/thyroglobulin conjugate. Immunofluorescence histochemistry with antiserum revealed a widely distributed system of axons and their terminals in the nervous system of the rat. Prominent networks of enkephalin-like immunoreactivity were found in some brainstem nuclei and in portions of the limbic forebrain. The myenteric plexus in the gastrointestinal tract also contained fluorescent fibers. The distribution of the positive immunofluorescence parallels the occurrence of enkephalin as revealed by biochemical techniques. Some areas known to have a high opiate receptor density were also shown to contain striking networks of enkephalin-like immunoreactivity. Such findings provide morphological support for the hypothesis that enkephalins are contained in nerve terminals close to opiate receptors.

Animals↗

Search for an endogenous ligand for the opiate receptor.

It was investigated whether there is an endogenous factor in the brain which binds to the opiate receptor in neural tissue. Extracts from rat brain were processed in different ways; fractions were assayed for ability to inhibit the receptor binding of dihydromorphine. There was no evidence for high-molecular weight substances or lipid soluble substances with such ability. On the other hand, processing of an acid water extract of brain except the cerebellum (which was negative) yielded an active fraction with receptor blocking activity. This fraction was heat stable, polyionic and had an apparent molecular weight of 1000-1 200 dalton. These and other characteristics indicate that it might well be a peptide. The factor inhibited binding to the opiate receptor in synaptic plasma membranes of rat brain and to the receptor of the guinea-pig ileum although it was less effective on the latter, particularly after long-term incubation. The interaction between the factor and dihydromorphine was reversible and apparently competitive.

Animals↗