Human alpha-thrombin increases the permeability of bovine pulmonary artery endothelial cell (CCL-209) monolayers. To determine if this increase is via an enzymatic or receptor-mediated mechanism, enzymatically active forms of alpha-thrombin and enzymatically inactive forms with cell binding activity were incubated with the monolayers. Enzymatic forms included alpha-thrombin and two digestion products, zeta-thrombin (chymotryptic product with 89% clotting activity) and gamma-thrombin (tryptic product). Enzymatically inactive forms included D-Phe-Pro-Arg-chloromethylketone-(PPACK) alpha-thrombin and diisopropylphosphorofluoridate-(DIP) alpha-thrombin. Cell binding activity of alpha- and PPACK-alpha-thrombin was demonstrated to be similar to each other and comparable to that cited in the literature for DIP-alpha-thrombin. gamma-Thrombin, on the other hand, did not compete for binding of 125I-labeled alpha-thrombin. All enzymatic forms of alpha-thrombin increased endothelial permeability as assessed by the clearance of 125I-albumin across the monolayers. Coincubation of PPACK, an enzymatic site inhibitor, with alpha- or gamma-thrombin prevented the increase in permeability, further indicating that alpha-thrombin increased permeability by its enzymatic activity. Both enzymatically inactive forms of alpha-thrombin with high-affinity binding activity had no effect on permeability. To further examine whether cell binding activity of alpha-thrombin contributed to the increased permeability, a sulfated COOH-terminal fragment of hirudin (hirugen) that binds to the anion-binding site of alpha-thrombin but, unlike hirudin, does not interact with the catalytic site was coincubated with alpha-thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Previous studies concerning ischemic priapism revealed that hypoxia alters the erectile and contractile responses of penis. But the effects of accompanying acidosis on those responses have not been fully evaluated or understood yet. We performed this study to elucidate the role of acidosis on the trabecular smooth muscle contractility like in ischemic priapism.Under the general anesthesia, 55 mature male cats were conditioned to systemic metabolic acidosis by hypoventilation by animal ventilator. The changes of intracavernous pressure (ICP) to erectogenic agents (acetylcholine, L-arginine, prostaglandin E 1 : PGE 1 ), erectolytic agents (epinephrine, thromboxane A 2 ; TXA 2 ), K channel-related drugs (pinacidil, 4-aminopyridine, tetraethylammonium; TEA, glibenclamide) and calcium ionophore were monitored at Set 1 (PO 2 b 60 mmHg, pH b 7.25), Set 2 (PO 2`3 0 mmHg, 7.25 b pH b 7.0), Set 3 (PO 2`3 0 mmHg, pH`7.0), and Set 4 (PO 2 b 60 mmHg, pH`7.0) in vivo.At Set 1 and Set 2, epinephrine, TXA 2 , and ionomycin decreased the ICP by acetylcholine or PGE 1 (n 9, P`0.01). The decrease of ICP was in order of epinephrine, TXA 2 and ionomycin. Acidosis reduced the increase of ICP to acetylcholine or PGE 1 (n 8, P`0.01), TXA 2 or ionomycin did not affect ICP under severe acidosis but epinephrine decreased ICP even under severe acidosis (n 7, P`0.05). Pretreatment of potassium channel blockers did not suppress the increase of ICP by erectogenic agents under acidosis (n 6, P`0.05). Pinacidil did not affect ICP under acidosis (n 6, P`0.01).These results suggest that acidosis impairs the contractile response of cavernous smooth muscle to erectolytic agents. It may be the results of the interference by [H ] with the intra and extracellular mechanisms that regulate the homeostasis of [Ca 2 ]. Conclusively, besides hypoxia, acidosis is another limiting factor of trabecular smooth muscle contractility like in ischemic priapism.

Despite extensive research into the toxicity of bisphenol A (BPA), no report of its effect on erectile function exists. We performed this study to investigate the effect of BPA on erectile function. New Zealand white rabbits were treated intraperitoneally with 150 mg=kg of BPA every other day for 12 days (cumulative dose of 900 mg=kg). Four and 8 weeks after administration of BPA, the contractions and relaxation of cavernosal tissue strips were significantly suppressed in the BPAtreated animals compared to the control animals. Histologically, thickening of tunica albuginea, subtunical deposition of fat and decreased sinusoidal space with consequent increase of trabecular smooth muscle content were observed in the BPA-treated animals. These results suggest that xenoestrogen BPA may affect the erectile function through evident histological changes of the penis.

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