Receptors classes

A subset of ion channels not gated by traditional neurotransmitters represents another receptor class. These iaclude potassium, calcium, sodium, and cychc adenosiae monophosphate (cAMP)-gated channels (14—16) for which a large number of synthetic molecules exist that alter ceUular function. 

The grouping of receptors oa the basis of sequeace homology has beea easiest ia the case of those receptor classes where pharmacological tools have eaabled the elucidatioa of fuactioa coasisteat with stmcture. 

The prolactin receptor, PER, which regulates milk production in mammals, belongs to the same receptor class as the growth hormone receptor. In addition to binding the hormone prolactin, PER also binds and is activated by growth hormone. The extracellular domain of PER forms a very stable 1 1 complex with growth hormone in solution this complex has been crystallized and its structure determined (Figure 13.21). We shall compare this structure with the 1 2 complex of the same hormone with GHR. 

A number of agonists can act through several receptor classes, e.g., ion channels and G-protein-coupled receptors. To set receptor subtypes permanently linked to ion channels ( ligand-gated ion channels) apart... 

The 5-HTx receptor class comprises five receptors (5-HT1a, 5-HT1b, 5-HTiD, 5-ht1E> and 5-HT1F) which, in humans, share 40-63% overall sequence identity and couple somewhat preferentially to Gi/o to inhibit cAMP formation (see Tables 1-3). The 5-htiE receptors are given a lower case appellation to denote that... 

HT4, 5-HTcAMP formation, yet they are regarded as distinct receptor classes because of their limited (<35%) overall sequence identities. This subdivision is arbitrary and may be subject to future modification. 

Besides classical receptor classes that bind endogenous or naturally occurring ligands and act via prototypical intracellular signaling cascades, a considerable number of transmembrane proteins are referred to as receptors albeit their natural ligands are unknown or they do not... 

Inhibition of EGF binding by palytoxin could be due to a decrease in receptor affinity, as in the case of TPA-type tumor promoters, and/or a decrease in receptor number. In Swiss 3T3 cells there are two classes of EGF receptors. The dissociation constants for the two EGF receptor classes were determined to be approximately 2 X 10 M and 2 x 10" M, corresponding to approximately 1 x 10 and 1 X 10 receptor molecules per cell, respectively (33). Scatchard analysis revealed that treatment of Swiss 3T3 cells with palytoxin, like PDBu, caused an apparent loss in high-affinity binding (Figure 2). However, in contrast to PDBu, palytoxin also caused a significant (approximately 50%) loss of low affinity EGF binding. 

Except for glycine, all fast transmitters act on both ion channel receptors and G-protein-coupled receptors. Within each receptor class, there may be several subtypes. 

FIGURE 3.2.2 Metabolic pathways of carotenoids such as p-carotene. CM = chylomicrons. VLDL = very low-density lipoproteins. LDL = low-density lipoproteins. HDL = high-density lipoproteins. BCO = p-carotene 15,15 -oxygenase. BCO2 = p-carotene 9, 10 -oxygenase. LPL = lipoprotein lipase. RBP = retinol binding protein. SR-BI = scavenger receptor class B, type I. 

Reboul, E. et al.. Lutein transport by Caco-2 TC-7 cells occurs partly by a facilitated process involving the scavenger receptor class B type 1 (SR-Bl), Biochem. J., 387, 455, 2005. 

Altmann, S.W. et al.. The identification of intestinal scavenger receptor class B, type 1 (SR-Bl) by expression cloning and its role in cholesterol absorption, Biochim. Biophys. Acta, 1580, 77, 2002. 

Krieger, M, 2001. Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. J Clin Invest 108, 793-797. 

Reboul, E, Klein, A, Bietrix, F, Gleize, B, Malezet-Desmoulins, C, Schneider, M, Margotat, A, Lagrost, L, Collet, X, and Borel, P, 2006. Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. J Biol Chem 281, 4739 4745. 

The first study was conducted to determine whether carotenoids and cholesterol share common pathways (transporters) for their intestinal absorption (During et al., 2005). Differentiated Caco-2 cells on membranes were incubated (16 h) with a carotenoid (1 pmol/L) with or without ezetimibe (EZ Zetia, an inhibitor of cholesterol transport), and with or without antibodies against the receptors, cluster determinant 36 (CD36) and scavenger receptor class B, type I (SR-BI). Carotenoid transport in Caco-2 cells (cellular uptake + secretion) was decreased by EZ (lOmg/L) as follows P-C and a-C (50% inhibition) P-cryptoxanthin and LYC (20%) LUT ZEA (1 1) (7%). EZ reduced cholesterol transport by 31%, but not retinol transport. P-Carotene transport was also inhibited by anti-SR-BI, but not by anti-CD36. The inhibitory effects of EZ and anti-SR-BI on P-C transport... 

In summary, Caco-2 cells studies strongly suggest that carotenoids interact with each other at the level of cellular uptake by the enterocyte. This phenomenon has been explained by the fact that the uptake of several carotenoids involves, at least in part, the same intestinal membrane transporter the scavenger receptor class B type ISR-BI (Reboul et al. 2005, van Bennekum et al. 2005, Moussa et al. 2008). 

Moussa, M. et al. (2008). Lycopene absorption in human intestinal cells and in mice involves scavenger receptor class B type I but not Nienmann-Pick Cl-like 1. J. Nutr. 138 1432-1436. 

X.-A. Li, W. B. Titlow, B. A. Jackson, N. Giltiay, M. Nikolova-Karakashian, A. Uittenbogaard, and E. J. Smart. High Density Lipoprotein Binding to Scavenger Receptor, Class B, Type I Activates Endothelial Nitric-oxide Synthase in a Ceramide-dependent Manner. J. Biol. Chem. 277 11058-11063 (2002). 

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