Relaxation of rat gastrointestinal smooth muscle by parathyroid hormone

In this study we investigated whether parathyroid hormone (PTH) can produce relaxation of gastrointestinal (GI) smooth muscle as it has been reported to do for vascular and uterine smooth muscle. Muscle tissue preparations from rat stomach, duodenum, ileum, or colon were mounted in a 37 degrees C tissue bath and perfused with oxygenated medium. Changes in isometric tension were recorded with a force-displacement transducer connected to a polygraph. Decreases in either resting tension or agonist-induced tension (0.5-1.0 microM acetylcholine or carbachol) were observed within 1-2 min of PTH addition and were reversible upon removal of the peptide. All GI regions tested were responsive to PTH. Synthetic rPTH-(1-34) (0.1-100 nM) produced a dose-dependent relaxation of both fundic (ED50 = 5.2 nM) and colonic (ED50 = 2.5 nM) muscle strips. At 100 nM, a 90% decrease in fundic tension and a 70% decrease in colonic tension were seen. At 100 nM, bPTH-(1-34), but not bPTH-(7-34) or rat calcitonin gene-related peptide, also was effective in relaxing fundic or colonic muscle. Similarly, in the fundic muscle, 500 nM bPTH-(3-34) alone was ineffective, but it inhibited the effect of 5 nM rPTH-(1-34) when both peptides were tested in combination. Likewise, 100 nM bPTH-(3-34) also inhibited the relaxation induced by 5, 10, or 100 nM bPTH-(1-34). The results show PTH to be highly effective in nanomolar concentrations in causing relaxation of GI smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)