VIP-induced alterations in cAMP and inositol phosphates in the lower esophageal sphincter.
Adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), and inositol phosphate (IP) levels were measured in thin tissue samples from the circular smooth muscle of the cat lower esophageal sphincter (LES) at 37 degrees C during vasoactive intestinal peptide (VIP)-induced relaxation. On exposure of in vitro LES circular muscle strips to 10(-6) M VIP at the same temperature, relaxation of spontaneous resting tone begins within 3-6 s, is half maximal at 30 s, and maximal at 1 min. VIP-induced changes in cAMP, cGMP, and IP metabolite levels were measured at 5 and 30 s after the addition of 10(-6) M VIP. At 5 s cAMP levels increased significantly with respect to time-matched unstimulated controls, whereas inositol 1,4,5-trisphosphate (1,4,5-IP3) decreased and these changes remained constant at 30 s. cGMP levels were unchanged at either 5 or 30 s after exposure to 10(-6) M VIP. These data suggest that VIP-induced relaxation is temporally linked to decreased 1,4,5-IP3 as well as increased cAMP levels.
Szewczak
S M
SM
Rhode Island Hospital, Providence.
Behar
J
J
Billett
G
G
Hillemeier
C
C
Rhim
B Y
BY
Biancani
P
P
D000818:Animals; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D007295:Inositol Phosphates; D014660:Vasoactive Intestinal Peptide; D007294:Inositol; D000242:Cyclic AMP; D006152:Cyclic GMP