Activation of beta-adrenergic receptors causes stimulation of cyclic AMP, inhibition of inositol trisphosphate, and relaxation of bovine iris sphincter smooth muscle. Biochemical and functional interactions between the cyclic AMP and calcium signalling systems.
We have investigated the interactions between the cAMP and inositol 1,4,5-trisphosphate (IP3)-Ca2+ signalling systems in the bovine iris sphincter by measuring the effects of beta-adrenergic and cholinergic muscarinic agonists and antagonists on cAMP formation, IP3 accumulation and muscle contraction-relaxation. (1) Addition of 5 microM isoproterenol (ISO) or forskolin (5 microM) consistently produced stimulation of cAMP (540%), inhibition of IP3 (34%) and complete relaxation of the muscle. The ISO effects were dose-dependent, with EC50 values for cAMP formation, IP3 inhibition and muscle relaxation of 2.8 X 10(-7) M, 3.4 X 10(-7) M and 0.45 X 10(-7) M, respectively. (2) Timolol, a beta-adrenergic antagonist, inhibited the ISO effects in a dose-dependent manner, with IC50 values for cAMP formation, IP3 accumulation and muscle relaxation of 1.8 X 10(-5) M, 3.2 X 10(-5) M and 2.2 X 10(-5) M, respectively. (3) The effects of ISO (0.5 microM) were time-dependent, and they clearly indicate a temporal relationship between the agonist-induced stimulation of cAMP, inhibition of IP3, and relaxation of the muscle. Within 15 sec following the addition of ISO, there was a marked increase in the level of cAMP, a decrease in IP3, and this was accompanied by an equally rapid relaxation of the muscle. (4) Addition of carbachol (CCh) to iris sphincter pretreated with ISO decreased cAMP formation and reversed muscle relaxation to complete contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Tachado
S D
SD
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta.
Akhtar
R A
RA
Abdel-Latif
A A
AA
D000818:Animals; D002118:Calcium / Q000502:physiology; D002417:Cattle; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors*; D007498:Iris / Q000378:metabolism / Q000502:physiology*; D009119:Muscle Contraction; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology*; D010277:Parasympathomimetics / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013566:Sympathomimetics / Q000494:pharmacology
D010277:Parasympathomimetics; D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D002118:Calcium