No abstract

A potent non-peptide ET receptor antngonisl, myriceron caffeoyl ester (50-235), was isolated from the bayberry, ,44yrica ccr~$m~. This compound selectively antagonized specific binding of ["'IlET-I, but not of [lz51]ET-3, to rnt cardiac membranes, ET-L-indud increase in the intracellular free calcium concentration in Swiss 3T3 fibroblasts. and ET-l-induced contraction of rat aortic strips. Thus, 50-235 is the first non-peptide ET,, receptor antagonist. This compound cnn be useful for studying the physiological role of cndothclin and exploring its role in various diseases.

The addition of porcine pncrcatir voup I phorpholipsc A: WA:-I) produced Y lranricnt contrastion followcd by n rclmxation in hslisal strips of prcinc ccrcbrul artcries. Its ED, value (2.3 RM) was almosf idcntir;ll10 the t& veluct3.9 nM) calculated from lhc spcrinc binding of 'zslWxlsd porcine PLA:-t in cultured porcine cerebral arterial smoolh murlc ccllr. Typcapscific action of PLAIs and homologousdcxnritization rlrongly impliratcd the involvcmcnt of PLA+sprcific sitar in the rcsponfe. The tnnrlcnt contraction was abolished by tratmcnt with indomcthacin as well IL by the removal of cndothclium. indiwting the dcpcndcncc of varoconrtrictor prosroglandins synrhcsizcd by PLA,-I in cndoihclium. Thr PLA,44nduccd relaxation rcspnsc wus also obscmxl in bovine and cat cerebral arteries. thus providin& P new aspect of PLAI-I as a VraoacGvc subntnncc.

No abstract

In A7r5 smooth muscle cell suspensions, 12-deoxyphorbol 13-isobutyrate (DPB) and phorbol 12,13-dibutyrate (PDB), active phorbol esters for protein kinase C (PKC), increased the intracellular Ca2+ concentration ([Ca2+]i), but 4 alpha-PDB, an inactive phorbol ester, did not. Digital images of the fura 2 fluorescence from single cells revealed that DPB caused elevation of Ca2+ in localized peripheral regions, followed by expansion of this elevated Ca2+ level throughout the cytoplasm. High K+ also induced a dynamic change of [Ca2+]i. DPB and high K+ increased the wrinkles and distortions in the flexible growth surface beneath the cells. In Ca(2+)-depleted media, DPB did not affect [Ca2+]i but substantially increased wrinkles. The increase could be eliminated by staurosporine, a specific inhibitor of PKC. DPB increased the particulate PKC activity in a concentration-dependent manner. These results suggest that PKC activation induces cellular contractions through two distinct mechanisms, one dependent on and another independent of the [Ca2+]i increase.