Receptor-Mediated Effects

H2 The H2 receptor mediates effects, through an increase in cycHc adenosine monophosphate (cAMP), such as gastric acid... 

The class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

Stable analogs of GTP and GDP can be used to study the role of the G-protein, as indicated above. Thus, stable GTP analogs enhance agonist-induced receptor-mediated effects and slow their reversal, as shown in Figure 7.6. Pertussis and cholera toxins can also be used to inhibit or activate certain G-proteins, as indicated. 

Monaca, C., Boutrel, B., Hen, R., Hamon, M. Adrien, J. (2003). 5-HTia/b receptor-mediated effects of the selective serotonin reuptake inhibitor citalopram, on sleep studies in 5-HTia and 5-HTib knockout mice. Neuropharmacology 28, 850-6. 

Roberts, C., Thomas, D. R., Bate, S. T. Kew, J. N. C. (2004). GABAergic modulation of 5-HT7 receptor-mediated effects on 5-HT efflux in the guinea-pig dorsal raphe nucleus. Neuropharmacology 46, 935-41. 

Labetalol appears to produce relaxation of vascular smooth muscle not only by a-blockade but also by a partial agonist effect at P2-receptors. In addition, labetalol may produce vascular relaxation by a direct non-receptor-mediated effect. 

Ruotsalainen S, Miettinen R, MacDonald E, et al The role of the dorsal raphe-serotonergic system and cholinergic receptors in the modulation of working memory. Neurosci Biobehav Rev 22 21-31, 1998 Rupprecht R, ReulJMHM, Trapp T, et al Progesterone receptor-mediated effects of neuroactive steroids. Neuron 11 523-530, 1993 Rush AJ, Beck AT, Kovacs M, et al Comparative efficacy of cognitive therapy and pharmacotherapy in the treatments of depressed outpatients. Cognitive Therapy Research 1 17-37, 1977... 

Fang, H Tong, W.D., Welsh, W.J. and Sheehan, D.M. (2003) QSAR models in receptor-mediated effects the nuclear receptor superfamily. J. Mol. Struct. THEOCHEM, 622 (1-2), 113-125. 

Adenosine deaminase catalyzes the hydrolytic deamination of adenosine and 2 -deoxyadenosine to inosine and 2 -deoxyinosine respectively. Inhibition of adenosine deaminase leads to an accumulation of its substrates which results in adenosine receptor-mediated effects. Most inhibitors are not reported to have antinociceptive properties, but 2 -deoxycoformycin was proven to have an inhibitory effect on pain transmission (Poon and Sawynok, 1999), and Fujisawa Pharmaceuticals claim adenosine deaminase inhibitors to be active against chronic pain. 

The Hi Receptor and its Ligands. The H receptor mediates effects, through an increase in cyclic adenosine monophosphate (cAMP). such as gastric acid secretion relaxation of airway smooth muscle and of pulmonary vessels increased lower airway mucus secretion esophageal contraclion inhibition of basophil, but not mas cell histamine release inhibition of neutrophil activation and induction or suppressor T cells. There is no evidence that the H- receptor causes significant modulation of lung function in the healthy human subject or in the asthmatic. 

We do not know whether the interactions between the presynaptic receptors occur on the level of the receptors or on a site beyond the receptor level, e.g. on the level of G proteins, ion channels or other second messengers. Such receptor interactions may explain drug interactions in vivo. They are also of importance for planning in vitro experiments. H3 receptor-mediated effects in superfused slice preparations are frequently small the inhibitory effect on NA and DA release can be increased by simultaneous blockade of the respective autoreceptor. There are even examples of H3 heteroreceptors which could only be identified if the respective autoreceptor was blocked3 12,36. 

As far as the inhibitory mechanism of H3-receptors is concerned, the effect of (R)a-methylhistamine is decreased by pretreatment with pertussis toxin and, like the 012-adrenoceptor- and Aj-adenosine receptor-mediated effects, it is potentiated by oo-conotoxin GVIA, a blocker of the N-type Ca channel (Endou et al., 1994). One may conclude from these findings that presynaptic histamine H3-receptors are probably coupled to a pertussis toxin-sensitive Gi/Go protein, which exerts a negative control on the neuronal Ca++-currents, that are responsible for the exocytotic release of noradrenaline. 

There are two types of histamine receptors HI receptors, which are blocked by agents such as diphenhydramine and other antiallergic compounds, and H2 receptors, which are blocked by cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), and nizatidine (Axid). Cimetidine has no effect on most 11, receptor-mediated effects, such as bronchoconstriction. 

NECA, although nonselective, remains the most potent A2B agonist so far (Brackett and Daly 1994 Feoktistov and Biaggioni 1997) and thus, characterization of A2B receptor-mediated effects is based mainly on negative results, i.e. the failure of CGS 21680 or of CPA to reproduce NECA elicited responses (Feoktistov and Biaggioni 1997). 

The concentration of adenosine in the PI receptor biophase and the balance between Ai and A2a receptor-mediated effects is influenced by the adenosine inactivation systems (ADA and the adenosine uptake carriers see Figure4d). Ai receptors are surface anchoring proteins for ecto-ADA, and binding of ecto-ADA to Ai recep-... 

Queiroz G, Talaia C, Genoa Ives J (2003a) Adenosine A2A receptor-mediated facilitation of noradrenaline release involves protein kinase C activation and attenuation of presynaptic inhibitory receptor-mediated effects in the rat vas deferens. J Neurochem 85 740-8 Queiroz G, Talaia C, Gonpalves J (2003b) ATP modulates noradrenaline release by activation of inhibitory P2Y receptors and facilitatory P2X receptors in the rat vas deferens. J Pharmacol Exp Ter 307 809-15... 

Kuzmin, A., Madjid, N., Terenius, L., Ogren, S. O., and Bakalkin, G. (2006). Big dynorphin, a prodynorphin-derived peptide produces NMDA receptor-mediated effects on memory, anxiolyticlike and locomotor behavior in mice. Neuropychopharmacology 31, 1928-1937. 

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