Evidence for the existence of inositol tetrakisphosphate in mammalian heart. Effect of alpha 1-adrenoceptor stimulation.
The time course of the effects of phenylephrine (10 mumol/l) on force of contraction and on inositol phosphates in electrically driven left auricles from rat hearts labeled with [3H]inositol was studied. All experiments were performed in the presence of propranolol (1 mumol/l) and LiCl (10 mmol/l). Products measured after separation with high-performance liquid chromatography were inositol 1-phosphate (1-IP1), inositol 1,4-bisphosphate (1,4-IP2), inositol 1,3,4-trisphosphate (1,3,4,-IP3), inositol 1,4,5-trisphosphate (1,4,5-IP3), and inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-IP4). All inositol phosphates increased after stimulation with phenylephrine. 1,4,5-IP3 was the first compound to rise maximally within 30 seconds; this rise was followed by an increase in 1,3,4,5-IP4 and 1,4-IP2 beginning within 2 minutes. The increase in 1,3,4-IP3 and 1-IP1 was slower and did not reach steady state within 15 minutes. The positive inotropic effect of phenylephrine was maximal after 5 minutes. It is concluded that the increase in the presumed second messengers 1,4,5-IP3 and 1,3,4,5-IP4 coincides with the positive inotropic effect after alpha 1-adrenoceptor stimulation. Since the increase in 1,4,5-IP3 precedes the increase in force of contraction, 1,4,5-IP3 may initiate the positive inotropic effect of alpha 1-adrenoceptor agonists and 1,3,4,5-IP4 maintains the increase in force of contraction.
Kohl
C
C
Abteilung Allgemeine Pharmakologie, Universität-Krankenhaus Eppendorf, Hamburg, FRG.
Schmitz
W
W
Scholz
H
H
Scholz
J
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; C081655:inositol-1,3,4,5-tetrakisphosphate; D010656:Phenylephrine; D015544:Inositol 1,4,5-Trisphosphate; C058097:inositol 1,3,4-trisphosphate