Receptor inactivation

In some cases, receptor inactivation, e.g., of the V2 vasopressin receptor, is mediated by agonist-induced enzymatic cleavage of the GPCR. This nonendocytic proteolysis is promoted by a plasma membrane-associated metalloprotease. Proteinase-activated receptors (PARs) such as the thrombin receptor also follow a distinctly different pathway. PARs require the enzymatic cleavage of their N terminus, and the newly generated N terminus activates the receptor. Once... 

Zachariou, V., Caldarone, B.J., Weathers-Lowin, A. et al. Nicotine receptor inactivation decreases sensitivity to cocaine. Neuropsychopharmacology. 24 576, 2001. 

Sawyer, G. W. and Ehlert, F. J. (1999) Muscarinic M3 receptor inactivation reveals a pertussis toxin-sensitive contractile response in the guinea pig colon evidence for M2/M3 receptor interactions../. Pharmacol. Exp. Ther. 289,464-476. 

The stndy of activating and inactivating GNASl mutations, therefore, has served to elucidate the tissue-specific regulation of GPCR signaling. G protein subunits and accessory proteins have a great hold over the activity of a mnltitude of receptors. Disruptions to the G a subunit, on one extreme, can resemble phenotypes caused by numerous constitutively active receptor variants, while on the other extreme they can resemble complex phenotypic patterns of tissne-specific receptor inactivation. 

Lesch KP, Mossner R (1999) 5-HT lA receptor inactivation anxiety or depression as amiuine experience. Int J Neuropsychopharmacol 2 327-331... 

For simpler catechols employed in plant chemical defense we have synthesized and studied more complex analogs into which biological-receptor-site-directing functionality has been integrated to examine the potential of these redox-sensitive systems for inactivating targeted receptors. These modified catechols are models for selective receptor inactivation. 

The not infrequent failure of the extent of attachment of photoaffinity labels to parallel receptor inactivation can be explained in several ways. First, in some membrane-bound receptor systems, receptor subunits are present in excess over the other components of the system. Second, the ligand might induce or take part in a photochemical reaction at the ligand binding site that does not culminate in covalent attachment. Ligand sensitized photooxidation can be prevented by irradiating the sample in the... 

Meller E, Puza T, Diamond J, Lieu HD, Bohmaker K. Comparative effects of receptor inactivation, 17 beta-estradiol and pertussis toxin on dopaminergic inhibition of prolactin secretion in vitro. J Pharmacol Exp Ther 1992 263 462-469. 

Glutamate receptor inactivation leading to Decreased excitatory neurotransmission (defense against excitotoxicity ) Stabilized intracellular [Ca2+]... 

Mineralcorticoid receptor inactivating mutations PHAl Trends Endocrinol Metab, 2004. 15(6) p. 264-70. 

CBl receptor inactivation suppresses reproductive hormone secretion (Wenger et al. 2001). Serum LH and testosterone (T) levels significantly decreased in mutant (CBi ) mice (Table 1). Results from this investigation also indicated that cannabinoids regulate neuroendocrine function through fhe activation of CBi... 

Receptor inactivation theory, initially proposed by Gosselin in 1977 has been widely disseminated by Kenakin (35)and to some degree is based on the two-state model originally proposed by Katz and Thesleff (41) for ion channels, specifically the Torpedo nicotinic receptor. where the multimeric receptor exists in active and inactive states, with ligand binding altering the equilibrium between these two states. Receptor inactivation theory reflects a synthesis of both occupancy and rate theories providing an alternative consideration for the study of the RL interaction. 

These dynamic simulations of receptors and G-proteins in the cell membrane were used to determine whether or not receptor inactivation significantly affects G-protein activation, and thus, presumably, calcium mobilization. Parameters for three test cases are listed in Table III. All test cases have equal numbers of G-protein and equal equilibrium receptor occupation. In test case 1, no receptors are blocked. In test cases 2 and 3, 59.5% and 74.4% of the receptors are blocked prior to ligand stimulation. 

Dopamine is an important neurotransmitter in the CNS in ganglia of the limbic system and of the pituitary gland. It regulates the involuntary motoric, psychic processes and neuroendocrine functions. Dopamine also figures as a transmitter in synapses of the kidneys. More than 7 subtypes of dopamine receptors are recognized (Table 1). Whereas stimulation of D1-receptors inactivates adenylyl cyclase, D4.7 receptors activate this enzyme. D3-receptor activation leads to the closure of Ca2+ channels. 

Leach K, Dahmee MK, Hammond ND, Sando JJ and Peatt WB (1979) Molybdate inhibition of glucocorticoid receptor inactivation and transformation. J Biol Chem 254 11884-11890. 

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