G-protein Effects on 3HRX821002 Binding to Alpha-2 Adrenoceptor in Rat Brain / 대한정신약물학회지

OBJECTIVE: This study is to explore the effects on specific bindings between [ 3H]RX821002, alpha-2 adrenergic receptor antagonist and alpha-2 adrenergic receptor in rat brain by G-protein modulation. METHODS: The radioligand binding receptor study was conducted with [ 3H]RX821002, a new alpha-2 adrenergic receptor antagonist, in the presence or absence of Gpp(NH)p and pertussis toxin. RESULTS: The alpha-2 adrenergic receptors were saturated with [ 3H]RX821002 in the fashion of the single binding site. The dissociation constant (Kd) was 0.70+/-0.30 nM, and maximum binding (Bmax) was 599.9+/-283.4 fmol/mg protein. The saturation study showed that the maximum binding (B max ; 668.0+/-50.1 fmol/mg protein) was increased and the dissociation constant (Kd ; 0.61+/-0.14 nM) was decreased significantly in the presence of Gpp (NH)p compared to those (B max ; 559.8+/-81.9 fmol/mg protein, Kd ; 0.87+/-0.14 nM) in the absence of Gpp (NH)p (by paired t-test ; B max, p=0.023, Kd, p=0.005). In the presence of pertussis toxin, the maximum binding (B max ; 617.0+/-58.5 fmol/mg protein) was increased significantly (by paired t-test ; B max, p=0.001) but the issociation constant (Kd ; 0.92+/-0.24 nM) was not decreased compared to those (B max ; 554.1+/-66.1 fmol/mg protein, Kd ; 0.89+/-0.24 nM) in the absence of pertussis toxin. CONCLUSION: These results confirm that the binding profiles between [ 3H]RX821002 and alpha-2 adrenergic receptors be modified by G-protein modulation. This suggests that the drug effects on receptors be influenced by various conditions such as G-protein modulation.

Natriuretic peptides in the rat ofactory system

The olfactory system plays an important role in the mobilization of animal behaviour, along with the sense of taste. These functions are mediated by a complex olfactory structure composed of peripheral (olfactory epithelium) and central (olfactory bulb) components. Several neuropeptides are synthesized in the olfactory system and are believed to be involved in olfactive processing. Recently, another bioactive substance, atrial natriuretic peptide (ANP), has been demonstrated in the olfactory system. ANP is a potent diuretic, natriuretic and vasorelaxant hormone which, originally, was isolated from mammalian atria, but its gene is expressed in many loci. ANP is only one member of the natriuretic peptide (NP) family, which includes two other peptides, BNP (brain natriuretic peptide) and CNP (C-type natriuretic peptide) derived from different genes. All three peptides show many common features. A high concentration of ANP-immunoreactive varicose fibers has been detected in the rat olfactory nerve layer and glomerular layer of the olfactory bulb (OB). An important group of perykarya and thin varicose fibers has been observed in the olfactory tubercle. We have demonstrated the presence of both ANP precursor and ANP gene transcript in the rat olfactory bulb. In addition to synthesizing ANP, the OB contains ANP transducing receptors coupled to guanylyl-cyclase system. The immunoreactive ANP has also been detected in the rat olfactory mucosa (OM), where ANP has been localized in secretory cells of Bowman's gland and in the cells of the epithelial layer. The relatively low concentration of ANP in OM (2.5 ng/mg protein) suggests a local role for ANP, a hypothesis which is strengthened by the presence of ANP high affinity receptors in this tissue. Although the role of ANP in the olfactory system is not yet clear, ANP has been shown to modulate olfactory bulb mitochondrial membrane activity and to be involved in the olfactive function.