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) have been shown to relax various types of smooth muscle, e.g. vascular, uterine and gastric. This study demonstrates that PTH and PTHrP both relaxed cholecystokinin octapeptide (CCK)-induced tension in guinea pig gallbladder strips. This relaxation was concentration-dependent. The use of PTHrP (7-34) blocked the relaxant effect of both agents. This suggested PTH and PTHrP were 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 protein kinase A, suggested that cAMP mediated the relaxant action of PTH and PTHrP. The use of iberiotoxin indicated that the high conductance Ca(2+)-activated 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.
Kline
L W
LW
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. lkline@ualberta.ca
Benishin
C G
CG
Pang
P K
PK
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002227:Carbazoles; D002766:Cholecystokinin / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005704:Gallbladder / Q000187:drug effects*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010455:Peptides / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction
D000470:Alkaloids; D015220:Calcium Channels; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010455:Peptides; D011506:Proteins; C073601:KT 5823; D009569:Nitric Oxide; C064719:iberiotoxin; D002766:Cholecystokinin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP