endorphins

endorphins , neurotransmitters found in the brain that have pain-relieving properties similar to morphine. There are three major types of endorphins: beta endorpins, found primarily in the pituitary gland; and enkephalins and dynorphin, both distributed throughout the nervous system. Endorphins interact with opiate receptor neurons to reduce the intensity of pain: among individuals afflicted with chronic pain disorders, endorphins are often found in high numbers. Many painkilling drugs, such as morphine and codeine, act like endorphins and actually activate opiate receptors. Besides behaving as a pain regulator, endorphins are also thought to be connected to physiological processes including euphoric feelings, appetite modulation, and the release of sex hormones. Prolonged, continuous exercise contributes to an increased production and release of endorphins, resulting in a sense of euphoria that has been popularly labeled "runner's high."

endorphins Peptides, peculiar to vertebrates, manufactured by the pituitary gland, which have analgesic properties similar to opiates (e.g. morphine), because of an affinity for the same receptors in the brain.

endorphins During the 1960s and early 1970s, it became apparent that opioid drugs such as morphine and heroin produced their profound actions in the body by interacting with specific receptors on the outer membrane of nerve cells. This raised the intriguing question of why the body goes to the trouble of synthesizing such receptor proteins. Surely it was not just on the off chance that a drug such as morphine might be administered. In 1975 the group in Aberdeen, Scotland led by Hans Kosterlitz and John Hughes, isolated from the pig brain two related molecules, the enkephalins, which bind to and activate opioid receptors. These enkephalins are short peptides, each comprising five amino acids. Although at first glance the enkephalins did not look similar in chemical composition to morphine, they proved to have a crucial component in common. We now know that the brain contains as many as thirteen such endogenous (internally generated) opioid peptides, which have come to be referred to collectively as ‘endorphins’.

There are three classically defined opioid receptor types, named the m, d, and k receptors, and each of the endorphins shows a different spectrum of activation (agonist action) at these different receptors. The endorphins function as inhibitory neurotransmitters and neurohormones: they are released from nerve cells to act on other cells that bear opioid receptors and thus dampen the activity of those cells.

To probe the physiological functions of the endogenous opioid systems, either antagonist drugs can be administered or transgenic mice lacking one or more of the receptors can be developed. From such studies it is evident that the endorphins play little part in our normal routine daily functions. If, in ordinary circumstances, one were to be given an opioid antagonist such as naloxone, little change would be observed. It is when the body is stressed that the endorphins are important. Then they are released to activate their receptors and help to protect the body. Thus endorphins interacting with the m and d receptors have been implicated in the inability of some accident victims to sense the severe pain that their injuries should be causing and also in the ‘high’ that is experienced following exercise. Endogenous opioids may also be responsible for part of the analgesia experienced during acupuncture therapy.

Recently a new, endogenous neuropeptide system, very closely associated with the endogenous opioid system, has been discovered. Unfortunately, at present the terminology used to label the receptor and its endogenous peptide agonist is still quite clumsy. The receptor is referred to as the ORL1 receptor, and the endogenous peptide that is an agonist at the receptor is called either nociceptin or orphanin FQ. The term ‘nociceptin’ derives from the initial belief that this peptide acts in the opposite direction to the endorphins in that, rather than being pain relieving, it actually enhances pain (cf. noxious, from the Latin noceo, to injure). It is becoming apparent that this is an oversimplification and that this peptide in some circumstances inhibits the action of morphine and the endorphins but in other circumstances can also itself suppress pain.

What is very exciting is that this new system appears to be involved in other important brain functions apart from the sensation of pain. The discovery that it may be involved in memory, anxiety, and appetite control make it an exciting new area for drug development. Several major pharmaceutical companies are currently developing non-peptide molecules (more stable and brain-penetrating than the peptides) that will act as agonists and antagonists at the ORL1 receptor, to advance our knowledge of the physiological and pathophysiological functions of this receptor. Hopefully this will result in the discovery of novel therapeutic agents.

G. Henderson