Receptors for Neuropeptides: Ligand Binding Studies
Edwin E. Daniel in Neuropeptide Function in the Gastrointestinal Tract, 2019
Recently, some highly selective opioid drugs have been used to characterize opioid receptors in various highly purified membranes isolated from canine small intestine.4,6[3H]-diprenorphine, a nonselective opioid antagonist ligand, bound with similar affinities to the deep muscular plexus, myenteric plexus,6 and submucous plexus4 (also see Table 2). Competition with subtype-selective opioid compounds revealed that both deep muscular and myenteric plexus contain about 40 to 45% μ- and δ-sites and 10 to 15% κ-sites. Submucous plexus had a higher proportion of μ-sites (64%) and fewer δ-sites (24%), and κ-sites again constituted a small proportion of binding sites (see Table 2). However, κ-sites were actually present since a relatively selective K-ligand, [3H]ethylketocyclazosin, bound to both deep muscular plexus (DMP), and myenteric plexus (MP) at a high- and low-affinity site (curvilinear Scatchard plot). In the presence of high concentrations (0.5 μM each) of an unlabeled cyclic penicillin analogue of enkephalin, DPDPE, and a morphiceptin analogue, PLO-17, together to shield μ- and δ-subtypes, high-affinity sites could still be demonstrated.6
CNS Receptors for Opioids
Edythe D. London in Imaging Drug Action in the Brain, 2017
The investigation of opioid receptor distribution by receptor autoradiography has closely followed the development of opioid receptor ligands with increasing selectivity for the different opioid receptor types. While early studies were limited to the characterization of opioid receptors due to the low selectivity of the radiolabeled opiate drugs available (e.g., naloxone, diprenorphine, and etorphine), the identification of new peptide ligands with selectivity for particular opioid receptor types permitted the characterization of their distinct distributions. The development of in vitro labeling methods was essential for the use of these new ligands due to their limited ability to enter the CNS after systemic administration. The first opioid receptor distribution studies used the method of in vivo labeling to measure the distribution of [3H]diprenorphine binding sites in rat brain (Pert et al., 1975). Subsequent studies (Atweh and Kuhar, 1977a, 1977b, 1977c) provided the first detailed map of opioid receptor distribution in the rat CNS. The discovery of endogenous opioid peptides (Huges et al., 1975) and the recognition of their preferential interaction with δ opioid receptors (Lord et al., 1977) were an impetus for the development of in vitro receptor autoradiography since these peptides are rapidly metabolized in the blood stream and do not penetrate the blood-brain barrier. The demonstration of the feasibility of in vitro receptor autoradiography (Young and Kuhar, 1979) provided the means for the analysis of the distribution of opioid receptor types.
Stimulus-Secretion Coupling: Receptors
Stephen W. Carmichael, Susan L. Stoddard in The Adrenal Medulla 1986 - 1988, 2017
The modulation of bovine adrenal medullary secretion by the opiate agonist etorphine and the opiate antagonist diprenorphine was investigated by Barron and Hexum (1986b). Etorphine inhibited the spontaneous outflow of [Met]enkephalin by approximately 10% but had no significant effect on the spontaneous release of catecholamines. Etorphine significantly decreased the secretory effect of acetylcholine. Diprenorphine had no significant effect on the spontaneous release of either enkephalins or catecholamines, but it reversed the inhibition of release caused by etorphine. Barron and Hexum (1986b) concluded that this supported the contention that opiates modulate the secretion of catecholamines and enkephalins from the adrenal gland.
Efficacy and mode of action of external trigeminal neurostimulation in migraine
Published in Expert Review of Neurotherapeutics, 2018
Jean Schoenen, Gianluca Coppola
Admittedly, abnormalities of the pgACC are not specific to migraine. In cluster headache, in particular, the pgACC was found hypometabolic outside of a bout but its metabolism increased during a bout [72]. The same authors using PET with the opioid receptor ligand [11C]diprenorphine found an inverse relationship between duration of the cluster headache disorder and opioid receptor availability in pgACC and ipsilateral hypothalamus [73]. In drug-resistant chronic cluster headache patients, we have shown in a FDG-PET study that metabolism in the pgACC is increased in responders to chronic ONS compared to nonresponders [61]. In migraine and cluster headache, both neurovascular disorders, it remains controversial whether the dysfunction of descending pain control systems is a primary causative phenomenon or secondary to repeated painful attacks. Interestingly, both cluster headache [74] and migraine [75] are accompanied by hypothalamic activation as a possible generator of an attack. The pgACC has strong connectivity with the hypothalamus [76], which might thus explain why it is involved in both disorders.
Related Knowledge Centers
- Ligand
- Partial Agonist
- Binding Selectivity
- Μ-Opioid Receptor
- Κ-Opioid Receptor
- Δ-Opioid Receptor
- Veterinary Medicine
- Opioid
- Analgesic
- Etorphine