The Opioid And Related Peptides

Soon after the initial description of opioid binding sites using morphine-like radioligands, several laboratories identified endogenous peptides within the brain that bind to these opiate receptors (Table I). These peptides were then termed "endorphins," connotating their endogenous morphine-like character. Although their actions are likely to be very diverse, the only ones examined in detail involve analgesia and all the opioid peptides are active analgesics.

A. Enkephalins

The first peptides identified were the two enkephalins (Table I). These pentapeptides shared the same first four amino acids, differing only by a leucine or methionine at the fifth position. They are the endogenous ligand for the delta opioid receptor. The enkephalins are present throughout the brain and have been implicated in many actions. It is interesting that the enkephalins are present at high concentrations in the adrenal medulla, where they are colocalized with adrenalin. They also have been identified in other, nonneuronal tissues, including immune cells and the testis.

B. Dynorphins

Additional peptides with opioid-like actions were subsequently isolated. Dynorphin A is a heptadeca-peptide that contains the sequence of [Leu5]enkephalin at its amino terminus (Table I). Dynorphin A is the endogenous ligand for the kappa1 receptor, although it retains high affinity for mu and delta receptors as well. Its actions were difficult to evaluate until highly selective, stable drugs were synthesized. These agents have established an important role for dynorphin A and its receptors in pain perception.

Table I

Opioid and Related Peptides

[Leu ]enkephalin [Met5]enkephalin Peptide E (amidorphin)

BAM 22 BAM 20 BAM 18 BAM 12 Metorphamide Dynorphin A Dynorphin B a-Neoendorphin b-Neoendorphin bh-Endorphin

Endomorphin-1 Endomorphin-2 Orphanin FQ/nociceptin Orphanin FQ2 Nocistatin

Tyr-Gly-Gly-Phe-Leu Tyr-Gly-Gly-Phe-Met

Tyr-Gly-Gly-Phe-Met-Lys-Lys-Met-Asp-Glu-Leu-Tyr-Pro-Leu-Glu-Val-Glu-Glu-Glu-Ala-Asn-Gly-Gly-Glu-Val-Leu

Tyr-Gly-Gly-Phe-Met-Lys-Lys-Met-Asp-Glu-Leu-Tyr-Pro-Leu-Glu-Val-Glu-Glu-Glu-Ala-Asn-Gly-Gly

Tyr-Gly-Gly-Phe-Met-Lys-Lys-Met-Asp-Glu-Leu-Tyr-Pro-Leu-Glu-Val-Glu-Glu-Glu-Ala-Asn

Tyr-Gly-Gly-Phe-Met-Lys-Lys-Met-Asp-Glu-Leu-Tyr-Pro-Leu-Glu-Val-Glu-Glu-Glu

Tyr-Gly-Gly-Phe-Met-Lys-Lys-Met-Asp-Glu-Leu-Tyr

Tyr-Gly-Gly-Phe-Met-Arg-Val

Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Gln-Phe-Lys-Val-Val-Thr Tyr-Gly-Gly-Phe-Leu-Arg-Lys-Tyr-Pro-Lys Tyr-Gly-Gly-Phe-Leu-Arg-Lys-Tyr-Pro

Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu

Tyr-Pro-Trp-Phe-NH2

Tyr-Pro-Phe-Phe-NH2

Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asp-Glu Phe-Ser-Glu-Phe-Met-Arg-Gln-Tyr-Leu-Val-Leu-Ser-Met-Gln-Ser-Ser-Gln Thr-Glu-Pro-Gly-Leu-Glu-Glu-Val-Gly-Glu-Ile-Glu-Gln-Lys-Gln-Leu-Gln

Breaking Bulimia

Breaking Bulimia

We have all been there: turning to the refrigerator if feeling lonely or bored or indulging in seconds or thirds if strained. But if you suffer from bulimia, the from time to time urge to overeat is more like an obsession.

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