Structure-linked latency of muscarinic receptors in axonal transport

AbstractMuscarinic receptors that accumulated above a ligature in rat sciatic nerves were labelled in vitro under isotonic conditions withN[3H]methylscopolamine. The addition of 0.005% of digitonin doubled the binding in proximal segments above and close to the ligature but not in the intermediary segments between two ligatures. Osmotic shock and freeze-thawing treatments also enhanced the binding. Digitonin did not affect the affinity of muscarinic receptors but revealed a greater number of sites by increasing the membrane permeability to the hydrophilic ligand. We conclude that presynaptic muscarinic receptors that undergo fast axonal transport in rat sciatic nerves exist under a latent form because they are associated with vesicles. This is the first demonstration of a structure-linked latency for receptors

Biosynthèse, localisation intracellulaire et transport des catécholamines

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

From receptor internalization to nuclear translocation. New targets for long-term pharmacology.

Receptors involved in intercellular communication at the cell surface share the capacity to desensitize through molecular and cellular mechanisms. Cellular desensitization is a rapid and dynamic process whereby membrane receptors internalize in response to an excess of agonists. The internalized receptors may recycle rapidly or undergo down-regulation when following a degradative pathway. However, receptor internalization does not necessarily mean degradation; it also represents the initial step of a retrograde signalling system whereby an "interiorized" message, the ligand-receptor complex, can be transported in contrast to second messengers, along axons or in the cytoplasm leading to long-term effects in the nucleus. Such "third messengers" have to undergo nuclear translocation to serve as transcriptional regulators in the control of gene expression. The "third messengers" are thus cytoplasmic proteins, including the receptor itself, which may be associated with internalized vesicles and released by mechanisms which have not yet been elucidated. They represent already good targets for the development of new drugs, and multi-targeting and synergistic approaches are likely to increase their usefulness

IL-1 beta-like Freund's adjuvant enhances axonal transport of opiate receptors in sensory neurons

Chronic pain and inflammation increase substance P in sensory fibres of peripheral nerves in which opiate receptors are known to undergo axonal transport. The aim of the present study was to evaluate a possible modulation of axonal transport of opiate receptors in peripheral nerves during inflammation. After intraplantar injection of Freund's adjuvant to rats, the accumulation of mu and kappa opiate receptors increased on both sides of ligature in sciatic nerves of the injected paw. The contralateral side was unaffected and may serve as control. When IL-1 beta was injected into rat paws, the axonal transport of opiate receptors was increased in a similar way. This suggests that IL-1 beta represents a major mediator to sensitize nociceptors during inflammation through a process requiring retrograde signals