Publisher Summary Studies of receptor binding generally employ highly radioactive ligand derivatives; however, knowledge of the biological activity of the radioactive derivative is essential for a complete interpretation of the binding data. This chapter describes the relation between biological activity and binding, physicochemical detection and assay of receptors, solubilization of membrane receptors, provides examples of membrane-localized receptors, affinity techniques, polyvalent hormone derivatives, and receptor studies, and theoretical mechanisms of hormone–receptor binding and action. The biological response toward many neurotransmitters and hormones, such as insulin, acetylcholine, and epinephrine is rapid both in onset and in the termination of action on removal of these agents; therefore, it may be anticipated that the initial hormone–receptor interaction will also be reversible. The chapter shows that progress has been made toward understanding the way by which hormones, via interactions with cell–surface receptors, modulate overall cellular function. This interaction is only the first in a presumably complicated series of protein–protein interactions within the plane of the cell membrane; the mechanism, whereby the ultimate signal is transmitted to the internal cellular milieu is undoubtedly an equally intricate process. The chapter is considered to be useful in delineating the challenge that the elucidation of these processes presents and in providing a basis and incentive for more discoveries in this field.

Membrane receptors and hormone action.

Acute adrenocorticotropic hormone stimulation of adrenal corticosteroidogenesis. Discovery of a rapidly induced protein.

ACTH like peptides and opiate receptors in the rat brain. Structure-activity studies

The pituitary—adrenal system plays an essential role in homeostatic functions Numerous aspects of stress-induced pituitary—adrenal activation in relation to peripheral mechanisms of adaptation have been studied since Selye’s first observations on the general adaptation syndrome some 40 years ago (Selye, 1950) Little attention, however, has been paid to the brain as a target for these hormones Clinical observations frequently commented on psychological changes in addition to electrophysiological alterations in hyper- as well as hypocorticism (Cleghorn, 1957; Von Zerssen, 1976) Many a laboratory experiment during the last decade, however, disclosed the implication of a number of pituitary and hypothalamic hormonal peptides on various brain functions The importance of these entities was revealed by observations on behavioral disturbances following extirpation of the pituitary gland in rats (de Wied, 1969); in animals with hereditary diabetes insipidus, which lack the ability to synthesize vasopressin (de Wied et al, 1975a); or in rats in which the action of vasopressin in the brain is neutralized by intraventricular administration of specific vasopressin antiserum (van Wimersma Greidanus et al, 1975a)

Behavioral effects of peptides

HUGHES et al.1 have reported the isolation and structure of two pentapeptides from porcine brain with opiate agonist activity in isolated systems. The structure of one of these peptides, Met5-enkephalin, is identical with the sequence of pituitary β-lipotropin (β-LPH) between residues 61–65 (refs 2–4). To prove the biological correlation of brain enkephalin and pituitary β-LPH, a series of lipotropin fragments, LPH-(61–69)-5, LPH-(61–76)-6 and LPH-(61–91)-peptides7–10, have been isolated and shown to have opiate agonist activity in vitro. Only few and controversial data have been available so far on the analgesic effect in vivo of the above or similar lipotropin fragments. Enkephalins have recently been reported to induce analgesia in vivo11,12. Our preliminary data5,13, however, seemed to contradict these observations, rather suggesting that some larger fragment(s) of β-LPH may have analgesic properties. We have therefore compared the analgesic effects of Met5-enkephalin and some lipotropin fragments containing the complete structure of Met5-enkephalin at their NH2-terminus. The results show that the in vivo effect is a function of the length of the peptide chain, Met5-enkephalin being the least and LPH-(61–91)-peptide the most potent. During the preparation of this paper we have become aware of the recent observation of Bradbury and coworkers10,14 on a strong analgesic activity of LPH-(61–91)-peptide.

Comparative study on analgesic effect of Met5-enkephalin and related lipotropin fragments.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2871%2980520-3

Peter Schiller

Papers

Isolated adrenal cells: Log dose response curves for steroidogenesis induced by ACTH1–24, ACTH1–10, ACTH4–10 and ACTH5–10