Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) relax cholecystokinin-induced tension in guinea pig gallbladder strips

Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) h ave been shown to relax various types of smooth muscle, e.g. vascular, uter ine and gastric. This study demonstrates that PTH and PTHrP both relaxed ch olecystokinin octapeptide (CCK)-induced tension in guinea pig gallbladder s trips. This relaxation was concentration-dependent. The use of PTHrP (7-34) blocked the relaxant effect of both agents. This suggested PTH and PTHrP w ere acting through the same receptor. The use of Rp-cAMPs, an inhibitor of cAMP activation of protein kinase A, and H-89, a selective inhibitor of pro tein kinase A, suggested that cAMP mediated the relaxant action of PTH and PTHrP. The use of iberiotoxin indicated that the high conductance Ca2+-acti vated potassium channels also mediated the actions of PTH/PTHrP. The use of KT5823, a selective blocker of protein kinase G, also decreased the amount of relaxation induced by PTH/PTHrP. This suggested that crosstalk between the two second messenger (cAMP and cGMP) systems occurred. (C) 2000 Elsevie r Science B.V. All rights reserved.