Receptors, adrenergic opioid

TABLE 23-3 Examples of proteins regulated by phosphorylation Enzymes involved in neurotransmitter biosynthesis Tyrosine hydroxylase Tryptophan hydroxylase Neurotransmitter receptors Adrenergic receptors Dopamine receptors Opioid receptors Glutamate receptors Many others... 

Stone LS, MacMillan LB, Kitto KF, Limbird LE, Wilcox GL (1997) The a2A adrenergic receptor subtype mediates spinal analgesia evoked by 02 agonists and is necessary for spinal adrenergic-opioid synergy. J Neurosci 17 7157-65... 

Fairbanks CA, Stone LS, Kitto KF, Nguyen HO, Posthumus IJ, Wilcox GL. o2C-Adrenergic receptors mediate spinal analgesia and adrenergic-opioid synergy. J Pharmacol Exp Ther 2002 300 282-290. 

In other instances such apparent hybrid activities could be missing or less prominent, as shows the example of epibatidine, a powerful alkaloid from the skin of several arrow poison frogs. Synthetic (+)- and natural (-)-epibatidine have potent agonist activity at ganglionic-type nicotinic receptors. The epibatidines have little or no activity at a variety of other central receptors, including opioid receptors, muscarinic receptors, adrenergic receptors, dopamine receptors, serotonin receptors, and GABA receptors [81]. 

Cionidine. Clonidine dampens sympathetic activity originating at the locus coeruleus by stimulation of presynaptic a2-adrenergic receptors in the sympathetic chain (Covey and Classman 1991 Hughes 1994). It appears to have some efficacy for alcohol and opioid withdrawal and thus was evaluated for treatment of nicotine withdrawal as well (Covey and Classman 1991 Hughes 1994). Several clinical trials used oral or transdermal clonidine in doses of 0.1—0.4 mg/day for 2—6 weeks with or without behavior therapy. Three meta-analytic reviews reported that clonidine improved quit rates (Covey and Classman 1991 Courlay and Benowitz 1995 Law and Tang 1995). 

Oj-adrenergic receptors 5-HTi serotonin receptors Mu, delta, and kappa opioid receptors Benzodiaepine receptors D-2 dopamine receptors... 

Opioids, benzodiazepines, barbiturates, corticosteroids, dopamine agonists (e.g., amantadine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole), H2-receptor antagonists, anticholinergics (e.g., diphenhydramine, trihexylphenidyl), P-adrenergic blockers, clonidine, methyldopa, carbamazepine, phenytoin, baclofen, cyclobenzaprine, lithium, antidepressants (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors), and interleukin-2... 

Jordan, B. A., Trapaidze, N., Gomes, I., Nivarthi, R., and Devi, L. A. (2001) Oligomerization of opioid receptors with beta 2-adrenergic receptors a role in trafficking and mitogen-activated protein kinase activation. Proc. Natl. Acad. Sci. USA 98, 343-348. 

Ca2+ channels Ginseng extract rapidly and reversibly inhibits high-threshold, voltage-dependent Ca2+ channels in micromolar doses (Nah and McCleskey 1994 Nah et al. 1995). This effect is mediated by a receptor linked to a pertussis toxin-sensitive G protein, but it is not through o2 adrenergic, GABAB, muscarinic, or opioid receptors (Nah and McCleskey 1994). Several ginsenosides inhibit Ca2+ currents by 16 to... 

Finally, a thorough receptor binding study by Raffa and colleagues (1998) showed that hypericin extracts had no effect at adrenergic (alpha or beta), adenosine, angiotensin, benzodiazepine, dopamine, bradykinin, neuropeptide Y, PCP, NMDA, opioid, cholecystokinin A, histamine HI, or nicotinic ACh receptors. Although comprehensive, this study did not look at the binding of any other hypericum constituents. 

While GRK2, 3, and 5, phosphorylation has been associated with agonist activation of many receptors (44,137), only discrete regions of phosphorylation that are attributable to one specific enzyme appear to be essential for desensitization (122). With respect to the P -adrenergic (138-141), the dopamine D, (122), the p-opioid (142), the 5-opioid (143), the aj -adrenergic (133), the Aj and adenosine (144-146), and the N-formyl peptide (134) receptors, the motifs may be located in the carboxyl tail. 

In case of the P -adrenergic receptor, phosphorylation of serine and threonine residues in the carboxyl tail can be shown to be involved in desensitization and internalization (141,156). Other GPCRs—such as the p- and 5-opioid receptors... 

---