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In order to investigate the mechanism underlying MgATP‐dependent recovery of ATP‐sensitive potassium (KATP) channels, we expressed Kir6.2/SUR2A (inwardly rectifying K+ channel subunit/sulfonylurea receptor) or C‐terminal‐truncated Kir6.2 (Kir6.2ΔC26) in COS7 cells (Green monkey kidney cells), and carried out inside‐out patch clamp experiments. After patch excision in ATP‐free internal solution, the activity of Kir6.2/SUR2A channels could be maximally recovered by the application of 5 mM MgATP. Subsequent application of 100 μM Ca2+ induced a rapid decay of Kir6.2/SUR2A activity to 11·6 ± 1·1 % (mean ± s.e.m.) of the control level (Ca2+‐induced run‐down; n= 64). MgATP (5 mM) recovered 99·4 ± 4·2 % (n= 13) of the Ca2+‐induced run‐down. Protein kinase inhibitors such as W‐7, H‐7, H‐8 and genistein did not inhibit this reaction. However, wortmannin, an inhibitor of phosphatidylinositol 3‐ and 4‐kinases, blocked the MgATP‐dependent recovery in a concentration‐dependent manner; the magnitudes of recovery were 35·7 ± 7·2 % (10 μM) and 4·3 ± 2·5 % (100 μM) of the Ca2+‐induced run‐down. MgUDP (10 mM) reversed the Ca2+‐induced run‐down of Kir6.2/SUR2A channels by 60·4 ± 7·6 % (n= 5). Wortmannin failed to modify this reaction. Kir6.2ΔC26 channels, which opened in the absence of SUR2A, were less sensitive to Ca2+; Kir6.2ΔC26 channels were inactivated to 44·8 ± 4·4 % (n= 14) by 100 μM Ca2+. MgATP recovered the Ca2+‐induced run‐down of Kir6.2ΔC26 by 89·8 ± 7·7 % (n= 9), and 100 μM wortmannin inhibited this reaction (1·8 ± 2 %, n= 7). Application of 10 μM phosphatidylinositol‐4,5‐bisphosphate (PI‐4,5‐P2) recovered the activity of Kir6.2/SUR2A channels after Ca2+‐induced run‐down (104·3 ± 6·4 %, n= 10). Even after the MgATP‐dependent recovery was blocked by 100 μM wortmannin, PI‐4,5‐P2 reactivated the channels (102·3 ± 8·6 %, n= 5). Similar results were obtained with Kir6.2ΔC26. These results suggest that the entity of MgATP‐dependent recovery may be membrane lipid phosphorylation rather than protein phosphorylation, and that synthesis of PI‐4,5‐P2 or phosphatidylinositol‐3,4,5‐trisphosphate may upregulate Kir6·2 channels.

While oxytocinase is known to exist in pregnancy serum and placenta, the present study describes the expression of the mRNA for this enzyme in a wide variety of other human tissues. Northern blot analysis was used to detect the mRNA, with a probe derived from a cDNA for oxytocinase/placental leucine aminopeptidase (P-LAP). Both the distribution and localization of immunoreactive oxytocinase/P-LAP protein have been determined immunohistochemically by use of an anti-P-LAP antibody in normal placental, fetal and adult tissues. In placental tissues, only syncytiotrophoblasts were stained positively. In both fetal and adult tissues, positive staining was obtained in vascular endothelial cells, gastrointestinal mucosal cells, epithelial cells of hepato-biliary, pancreato-biliary, bronchial-alveolar and renal tubular systems as well as islet cells of pancreas and neurons in the central nervous systems. Sweat-gland cells, seminal vesicles and prostate gland in the adult, as well as adipocytes and skeletal muscle cells in the fetus were also stained. The widespread distribution of P-LAP suggests its involvement in a variety of physiological events not restricted to the regulation of the amounts of bioactive peptides such as arginine vasopressin (AVP) and oxytocin (OT) in pregnancy. The presence of P-LAP in syncytiotrophoblasts supports the idea that P-LAP in pregnancy serum is derived from the placenta.

This paper reexamines the main findings of Cardarelli et al. (2002), andContenaro andVidal (2006), who show that regional asymmetries undermine the implicit collusion of tax coordination in a repeated game model of capital tax competition. In particular, this paper investigates how increasing regional differences in the per capita capital endowments and/or production technologies affect the willingness of each region to cooperate in achieving tax coordination. It is shown not only that there may exist cases where tax coordination is facilitated with an increase in regional asymmetries increase and the greater the degree of asymmetry in terms of the net capital exports of the regions, but also that the higher the cooperation of the regions with respect to the sustenance of tax coordination.

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