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1 The vascular actions of the proteinase-activated receptor-2-activating peptides (PAR 2 APs), SLIGRL-NH 2 (SL-NH 2 ) and SLIGKV-NH 2 (KV-NH 2 ) as well as the reverse-sequence peptide, LSIGRL-NH 2 (LS-NH 2 ) and an N-acylated PAR 2 AP derivative, trans-cinnamoyl-LIGRLO-NH 2 (tcLI-NH 2 ), were studied in rat intact and endothelium-denuded artery ring preparations, primarily from the pulmonary artery (RPA). 2 In RPA rings with but not without a functional endothelium, SL-NH 2 (but not LS-NH 2 ) caused either an endothelium-dependent relaxation (at concentrations: 510 mM) or (at higher concentrations: 410 mM), an endothelium-dependent contraction. No contractile response was observed in endotheliumdenuded preparations, that otherwise contracted in response to the PAR 1 AP, TFLLR-NH 2 . 3 The endothelium-dependent contractile response to SL-NH 2 was not blocked by the a-adrenoceptor antagonist prazosin, the endothelin antagonist BQ123, the angiotensin II antagonist DuP753, by tetrodotoxin; nor by the enzyme inhibitors, N o -nitro-L-arginine-methylester (NO-synthase), indomethacin (cyclo-oxygenase), SKF-525A (epoxygenase) and MK886 (leukotriene synthesis inhibitor). 4 In the relaxation assay, KV-NH 2 was 5 fold less potent than SL-NH 2 , whereas in the contractile assay KV-NH 2 was about equipotent with SL-NH 2 . However, the maximal contractile response to KV-NH 2 was lower than that of SL-NH 2 . 5 The PAR 2 AP analogue, tcLI-NH 2 , was as active as SL-NH 2 in the relaxation assay but was inactive as a contractile agonist in the endothelium-intact RPA. 6 The relaxant responses caused by SL-NH 2 and trypsin, as well as the contractile response caused by SL-NH 2 , did not desensitize in the course of repeated exposures of the tissue to agonist; whereas the contractile response to trypsin, only observed at concentrations greater than 30 u ml 71 , was desensitized by previous exposure of the tissue to either thrombin or trypsin. 7 In a contractile assay, where the tissue was desensitized to a concentration of trypsin that would otherwise cause a relaxant response, the preparation still contracted in response to SL-NH 2 . However, the trypsin-desensitized preparations were no longer contracted by thrombin. 8 From the cross-desensitization by thrombin of the contractile response to trypsin (and vice versa), we concluded that the contractile e ect of trypsin was due to activation of the thrombin receptor and not PAR 2 . 9 We concluded that the endothelium-dependent contraction caused by high concentrations of SL-NH 2 is due to an as yet unidenti®ed contracting factor; whereas the endothelium-dependent relaxation response observed at low concentrations of SL-NH 2 (410 mM) is mediated by nitric oxide. 10 The distinct structure activity pro®les for the contractile response (potency of KV-NH 2 4SL-NH 2 ) compared with the relaxant response (potency of KV-NH 2 55SL-NH 2 ); the contractile responsiveness to SL-NH 2 of an endothelium-intact RPA preparation, that did not contract in response to trypsin; and the lack of contractil...

1 The contractile actions of the proteinase-activated receptor-2-activating peptides (PAR 2 APs), SLIGRL-NH 2 (SL-NH 2 ), SLIGKV-NH 2 (KV-NH 2 ), trans-cinnamoyl-LIGRLO-NH 2 (tc-NH 2 ), and the PAR 1 -AP, TFLLR-NH 2 (TF-NH 2 ) as well as trypsin and thrombin were studied in endotheliumdenuded and intact human umbilical vein (HUV) ring preparations. 2 In HUV rings with, but not without an intact endothelium, PAR 2 APs caused a concentrationdependent contractile response, whereas LSIGRL-NH 2 trypsin and PAR 1 APs were inactive. The contractile response was not aected by the endothelin ET A receptor antagonist, BQ123, the cyclooxygenase inhibitor, indomethacin, the leukotriene synthesis inhibitor, MK886, or the epoxygenase/P450 inhibitor, SKF-525A. Other pharmacological antagonists (prazosin, Losartan 1 ) were similarly inactive. 3 The order of potencies of the PAR 2 APs to cause a contraction in the endothelium-intact preparation was: SL-NH 2 44KV-NH 2 5tc-NH 2 . 4 Using an endothelium-free rat aorta ring as a reporter tissue, surrounded with endothelium-intact HUV as a donor tissue in a`sandwich assay,' we also monitored the ability of SL-NH 2 , TF-NH 2 , trypsin and thrombin to release either contractile (EDCF) or relaxant (EDRF) factors. 5 In the`sandwich assay' done in the presence of L-NAME (0.1 mM), the endothelium-intact HUV tissue (but not endothelium-denuded HUV) released a contractile factor (EDCF) in response to SL-NH 2 (50 mM) but not to trypsin or LSIGRL-NH 2 . The SL-NH 2 -mediated release/action of the EDCF was not aected by BQ123, indomethacin, MK886 or SKF-525A. 6 In the`sandwich assay', trypsin (4 ± 10 nM), SL-NH 2 , KV-NH 2 and tc-NH 2 caused the release of a relaxant activity (EDRF) from the endothelium-intact (but not the denuded) HUV preparation. The release of EDRF was blocked by 0.1 mM o nitro-L-arginine-methylester (L-NAME). Neither thrombin (10 u ml 71 , 100 nM) nor TF-NH 2 (50 mM) were active in this EDRF-release assay. 7 The relative potencies of the PAR 2 agonists for causing the release of EDRF in the HUV sandwich assay were: trypsin44SL-NH 2 44tc-NH 2 4KV-NH 2 . This order of potencies diered from the one observed for the same agonists in the HUV contraction assay (above) and in an intracellular calcium signalling assay, conducted with cloned human PAR 2 that was expressed in cultured rat kidney KNRK cells: trypsin44SL-NH 2 =tc-NH 2 4KV-NH 2 . 8 We conclude that PAR 2 APs (but not PAR 1 APs) via a receptor distinct from PAR 2 , can cause a contractile response in endothelium-intact HUV tissue via the release of a diusable EDCF, that is dierent from previously recognized smooth muscle agonists (e.g. prostanoid metabolites, endothelin, noradrenaline, angiotensin-II, acetylcholine).

Cellular automata (CAs) are dynamical systems which exhibit complex global behavior from simple local interaction and computation. Since the inception of cellular automaton (CA) by von Neumann in 1950s, it has attracted the attention of several researchers over various backgrounds and fields for modelling different physical, natural as well as reallife phenomena. Classically, CAs are uniform. However, non-uniformity has also been introduced in update pattern, lattice structure, neighborhood dependency and local rule. In this survey, we tour to the various types of CAs introduced till date, the different characterization tools, the global behaviors of CAs, like universality, reversibility, dynamics etc. Special attention is given to non-uniformity in CAs and especially to non-uniform elementary CAs, which have been very useful in solving several real-life problems.

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