Receptor response

Agonist An agonist is a receptor ligand mediating a receptor response (intrinsic effect). 

Toxic reactions occur by several mechanisms activation of metabolism, production of reactive intermediates and subsequent reactions with cell macromolecules, changing receptor responses, or through abnormal defence reactions. Several compounds cause toxicity by mimicking the organism s own hormones or neurotransmitters, or activating the body s endogenous receptors in some non-physiological way. ... 

I he diverse range of phannacological actions of this structural class documents the belief that the naphthalene nucleus consists of a scaffold upon which vanous functional groups can be arranged tnd that the action elicited is a consequence of receptor response to the kind and spatial arrange ment of these functions... 

FIGURE 5.6 Calcitonin receptor responses, (a) Real-time melanin dispersion (reduced light transmittance) caused by agonist activation (with human calcitonin) of transfected human calcitonin receptors type II in melanophores. Responses to 0.1 nM (filled circles) and lOnM (open circles) human calcitonin, (c) Dose-response curves to calcitonin in melanophores (open circles) and HEK 293 cells, indicating calcium transient responses (filled circles). 

FIGURE 5.10 Effects of co-expressed G-protein (G ) on neuropeptide NPY4 receptor responses (NPY-4). (a) Dose-response curves for NPY-4. Ordinates Xenopus laevis melanophore responses (increases light transmission). Ordinates logarithms of molar concentrations of neuropeptide Y peptide agonist PYY. Curves obtained after no co-transfection (labeled 0 jig) and co-transfection with cDNA for Gai6. Numbers next to the curves indicate jig of cDNA of Ga]g used for co-transfection, (b) Maximal response to neuropeptide Y (filled circles) and constitutive activity (open circles) as a function of pg cDNA of co-transfected G g. 

This method can also be employed with the operational model. Specifically, the operational model defines receptor response as... 

Paired t-tests Changes in constitutive calcitonin receptor responses with 100 nM AC512. 

Danner S, Lohse MJ (1999) Regulation of p-adrenergic receptor responsiveness. Rev Physiol Biochem Pharmacol 136 183-223... 

Peroxisome Proliferator-Activated Receptors. Figure 3 Transcription of PPAR target genes. A schematic representation of the transcription of PPAR-regulated genes in the absence (a) and presence (b) of PPAR ligand. Abbreviations PPAR-RE, peroxisome proliferator-activated receptor-response element RNA Pol II, RNA polymerase II TATA-BP, TATA-binding protein. 

There is a good deal of evidence that the therapeutic effects of antidepressants could involve adaptive changes in 5-HTia receptors. Postsynaptic 5-HTia receptor responses became implicated because the hyperpolarisation of hippocampal CA3 pyramidal neurons that follows ionophoretic administration of 5-HT was found to be increased after chronic treatment with most (but not all) antidepressants (Chaput, de Montigny and Blier 1991). Others suggested that antidepressants attenuate postsynaptic 5-HTja responses because the hypothermia, evoked by their activation, is diminished by antidepressants (Martin et al. 1992). 

Decreases in / -receptor response were investigated when it was found that elderly patients taking... 

Decrease baroreflex sensitivity Decrease -receptor response Decrease 2 -receptor response Increase sensitivity to barbiturates Decrease glucose tolerance... 

The changes in -receptor response observed in some elderly patients have not yet been found to have any clinical significance. Theoretically, this decrease should result in an increase in the amount of norepinephrine being released from nerve terminals, but this has not yet been demonstrated [115,116]. 

Figure 4 Dose-response curves for the potentiation by brucine of ACh wholecell Mi muscarinic receptor responses. (A) Brucine (10-4 M) enhanced the potency of ACh to increase cAMP accumulation in Mi CHO cells by 2.6-fold. (B) Brucine (100 pM) produced a 3.0-fold increase in ACh potency in Ca2+ response to ACh. (From Ref. 9.)...

RPE expresses several receptors responsible for lipoprotein uptake, including lipoprotein receptors LDL receptor (LDLR) (Tserentsoodol et al., 2006b), VLDL receptor (VLDLR) (Hu et al., 2008), as... 

Ziouzenkova, O., G. Orasanu, G. Sukhova et al. 2007b. Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Mol Endocrinol 21( 1) 77—88. 

Ziouzenkova, O. and J. Plutzky. 2008. Retinoid metabolism and nuclear receptor responses New insights into coordinated regulation of the PPAR-RXR complex. FEBS Lett 582(1 ) 32—38. 

Forbes et al. saw a slight up-regulation of Connexin 43 in PC-3 cells (androgen unresponsive) with pure lycopene treatment but no Connexin 43 expression (with or without lycopene) in the highly metastatic PC-3MM2 variant (Table 21.2) indicating that with increasing metastatic conversion either the ability to turn on Connexin 43 is lost and/or the receptors responsive to lycopene are lost (Forbes et al. 2003). 

Bull, E.J., Hutson, P.H., and Fone, K.C., Reduced social interaction following 3,4-methylene-dioxymethamphetamine is not associated with enhanced 5-HT 2C receptor responsivity, Neuropharmacology 44(4), 439 148, 2003. 

Chou WY, Stewart MJ, Kruijer W, Crabb DW. The retinoid X receptor response element in the human aldehyde dehydrogenase 2 promoter is antagonized by the chicken ovalbumin upstream promoter family of orphan receptors. Arch Biochem Biophys 2000 280 192-200. 

Buprenorphine does not cause dependence in humans [96]. Unbke morphine, buprenorphine desensitizes the /< receptor coupling to adenylyl cyclase [80]. The desensitization occurs in the absence of any receptor internalization or downregu-lation [80]. The desensitization of the /x receptor may be the underlying basis for why buprenorphine does not cause a heightened adenylyl cyclase activity in // receptor-responsive cells. Buprenorphine s unique cellular regulation of the // receptor may explain its ability to be a non-addictive analgesic as well as its usefulness in treating opiate dependence. 

Changing the amino acid sequence of the cloned receptors by mutating nucleotides within the receptor cDNAs has proven to be an effective mechanism by which to identify structural features of the receptors responsible for their unique functional properties. In particular, site-directed mutagenesis has been employed to determine the ligand binding domains of each opiate receptor. 

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