Abstracts
1999 Digestive Disease Week

# 2139 THE DIRECT PRORELAXING EFFECT OF THYROXINE (T4) ON SPHINCTER OF ODDI (SO) IS MEDIATED VIA K+-CHANNEL REGULATION
Johanna Inkinen, Med Sch, Tampere Univ, 33800 Tampere Finland; J Sand, Univ of Tampere, Tampere Finland; P Aryola, Univ of Tampere Hosp, Tampere Finland; I Porsti, I Nordback

Background: Previously we have shown that there is an increased prevalence of diagnosed hypothyroidism in common bile duct stone (CBD) patients, compared to gall bladder stone patients or age, sex and hospital admission adjusted controls. We have also shown that T4 has an inhibitory effect on SO contractility. This inhibitory effect is similar between T4 and triiodothyronine, but is weak or lacks in steroid hormones, and is not mediated via adrenergic or NO-ergic mechanisms. The present study was done to test the mechanism of the effect of T4 on the SO smooth muscle by testing the effect of K+-channel blocker on the T4 induced SO prorelaxation. Methods: For ex vivo studies 1.5 mm SO rings (n=60) were prepared from anesthetized pigs and placed between two hooks in oxygenated physiologic salt solution at 37oC. SO contraction was measured with isometric force displacement transducers and registered on a polygraph. Each SO ring was first tested with KC1 (125 mM), and then studied with acetylcholine (ACh; 10 mM or 100 mM) and histamine (Hist; 10 mM or 100 mM) without and with T4 (10-10, 10-8 M), with T4 (10-10, 10-8 M) plus glibenclamide (10 mM), glibenclamide (10 mM) alone. Results: ACh and Hist induced contractions in the SO rings of 726±64 mg, and 773±67 mg, respectively (mean±SEM). The addition of T4 decreased the ACh and Hist induced contractions by a mean of 37%-44% (p<0.001) and 54%-56% (p<0.001), respectively, as compared to the contractions without T4. K+-channel blocker glibenclamide totally reversed the T4 induced inhibition of contraction. Without T4 glibenclamide did not change the SO contractility to ACh and Hist. Conclusion: The prorelaxing effect of physiological concentrations of T4 on SO is totally reversed by K+-channel blocker glibenclamide. However, glibenclamide does not have any effect of its own on the SO contractility. Thus this prorelaxing effect of T4 seems to be mediated by the effect on K+-channels.

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