The effect of serotonin [5-hydroxytryptamine (5-HT)] on pial venous tone of the pig was examined using in vitro tissue bath techniques. Isolated pial venous rings exhibited spontaneous rhythmic contractions (SRC) on mechanical stretching and/or applications of several vasoactive substances, including norepinephrine. On the other hand, KCl induced sustained active muscle tone (SAT) without SRC. The SRC induced by mechanical stretching were not affected by tetrodotoxin, nitro-L-arginine, alpha- and beta-adrenergic, histaminergic, and muscarinic receptor antagonists, indicating that the SRC in porcine pial veins are of myogenic origin. The SRC induced by stretching or applications of vasoactive substances and SAT induced by KCl were inhibited by 5-HT in a concentration-dependent manner. The inhibition was prevented by methysergide and methiothepin but not by ketanserin, propranolol, 3 alpha-tropanyl-1H-indole-3-carboxylic acid ester, hemoglobin, or nitro-L-arginine. The SRC and SAT were inhibited by 5-carboxamidotryptamine (5-CT), 8-hydroxy-2-di-N-propylaminotetralin HBr (8-OHDPAT), 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP), and 5-methoxytryptamine (5-MT), but not by sumatriptan, alpha-methylserotonin, or 2-methylserotonin. On the other hand, 5-CT, 8-OHDPAT, TFMPP, 5-MT, and sumatriptan constricted the porcine pial arteries exclusively. In 15% of pial venous preparations examined, 5-HT at low concentrations induced ketanserin-sensitive constrictions. These results indicate that the porcine pial venous smooth muscle contains multiple subtypes of 5-HT receptors. The 5-HT inhibition of SRC and SAT is predominant and is mediated by 5-HT1-like receptors, which, however, do not seem to correspond to 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT1E, or 5-HT1F receptor subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)

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This study aimed to examine the eŠects of banana juice on levodopa bioavailability in rats. When a levodopa preparation (EC-Doparl tablets) was orally administered with banana juice made by mixing with a fresh banana and water, there were signiˆcant decreases in C max (17.4±2.5 vs. 8.6±3.1 mg/ml; a＝0.05) and AUC (1882.8±49.2 vs. 933.5± 286.6 mg・min/ml; a＝0.05) for levodopa. On the other hand, administration of the levodopa preparation with a commercial beverage containing 10％ banana juice resulted in no signiˆcant change in C max or AUC. These results indicate that concomitant intake of levodopa preparations with banana juice, but not with a commercial banana beverage, may cause a drug-food interaction reducing levodopa bioavailability, and we should pay attention to such interactions during levodopa therapy for patients with Parkinson's disease.

ABSTRACT-The effects of tiropramide hydrochloride on Ca 2+ induced contraction, cytoplasmic free Ca 2+ levels and tissue cyclic AMP concentrations were investigated to elucidate the mechanisms of its antispasmodic action in the isolated detrusor from rats. Tiropramide inhibited the Ca 2+ (3 mM) induced contractions of the isolated urinary bladder depolarized in a Ca2+free medium, and the IC50 value was 3.3 X 10-6 M. When tiropramide was added during the sustained phase of the K+ (60 mM) contracture, IC50 values of tiropramide for the contraction and the increased fluorescence were 1.9 X 10-5 M and 16.4 X 10-5 M, respectively. On the other hand, the IC50 values for the K=induced con traction and fluorescence after pretreatment of the isolated urinary bladder with tiropramide were 2.1 X 10-5 M and 2.6 X 10-5 M, respectively. Tissue cyclic AMP levels at 1 min after addition of 10-5 M tiropramide were significantly increased. Papaverine, IBMX or forskolin potentiated the inhibitory effect of tiropramide on carbachol-induced contraction and its cyclic AMP-elevating effect. However, a good correlation between the degrees of potentiation of the inhibitory effect and the increase in cyclic AMP levels was not observed. The present results suggest that the smooth muscle relaxant activity of tiropramide in the isolated detrusor from rats may be intimately associated with predominant inhibition of Ca2+ influx and, to a lesser extent, an increase in intracellular cyclic AMP levels.

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