Urocortin hyperpolarizes stomach smooth muscle via activation of Ca2+-sensitive K+ currents.
The effect of urocortin (Uro), a recently discovered neuropeptide with selectivity towards corticotropin-releasing hormone type 2 receptor, was tested on whole cell currents expressed by guinea-pig gastric antrum smooth muscle cells. Uro (1 pmol/l-1 nmol/l) caused a concentration-dependent increase of Ca2+-sensitive K currents (I(K)) up to 500% as compared to control currents and did not affect the kinetics and voltage-dependence of inward Ca2+ currents. The I(K)-increasing effect of Uro was fully antagonized by preliminary emptying of intracellular Ca2+ stores with ryanodine and cyclopiazonic acid, as well as by bath application of selective blockers of adenylyl cyclase and cAMP-dependent protein kinase (PKA), but not by inhibitors of guanylyl cyclase, cGMP-dependent protein kinase, and protein kinase C. Comparable I(K) increase was obtained by forskolin (activator of adenylyl cyclase), Sp-cAMPS (activator of PKA), or by intracellular application of the catalytic subunit of PKA. It was concluded that Uro binds to a selective receptor in antral smooth muscle cells where it stimulates I(K) via PKA-dependent increase of Ca2+ concentration near the plasma membrane due to enhanced release from intracellular calcium stores.
Institute of Biophysics, Bulgarian Academy of Sciences, Sofia.
P S
PS
Petkova-Kirova
H S
HS
Gagov
D B
DB
Duridanova
D000818:Animals; D002118:Calcium / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D054832:Urocortins
D015221:Potassium Channels; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D002118:Calcium