Pharmacology In Vitro

When the efficacy of biphalin-stimulated G protein activation was examined (Table 3) in delta opioid receptor-transfected CHO cells, an efficacy ratio of 0.42 was determined as compared with deltorphin-II and DPDPE, the latter a reference delta-selective agonist. Such low efficacy values suggest that bipha-lin does not efficiently stimulate the G protein through the delta receptor [9]. Relative affinities of biphalin and morphine for mu, delta, and kappa binding sites in guinea pig brain membranes are shown in Table 4.

Shen and Crain [13] tested the effects of biphalin on naive and chronic morphine-treated dorsal root ganglion (DRG) neurons in cell culture. At low (pM-nM) concentrations, most mu, delta, or kappa opioid peptides as well as morphine and other opioid alkaloids elicit dose-dependent excitatory prolongation of the calcium-dependent component of the action potential duration (APD) of many mouse sensory DRG neurons. In contrast, application of the same opioids at higher (aM) concentrations results in inhibitory shortening of the APD [14]. Biphalin at a low concentration elicits only dose-

TABLE 3 Relative Efficacies of Biphalin and Delta-Selective Agonists at the WildType Cloned Human Opioid Receptor

Agonist

TABLE 3 Relative Efficacies of Biphalin and Delta-Selective Agonists at the WildType Cloned Human Opioid Receptor

Agonist

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