title: Dynamic changes of myocardial inositoltrisphosphate and cyclic nucleotides: relationship to contractile response in the perfused working rat heart after adrenergic and muscarinic agonist stimulation.
abstract: Initial and late effects by adrenergic and muscarinic agonists on inositol trisphosphate (IP3) and cyclic nucleotide levels were determined and correlated to mechanical response in perfused rat hearts. Forty-three rat hearts were perfused with Krebs-Henseleit buffer in a modified Langendorff apparatus as a working preparation. The hearts were perfused as controls (n = 11), or with noradrenaline (10(-6) mol l-1) (n = 21), or with carbachol (3 x 10(-7) mol l-1) (n = 11) added to the perfusion buffer. The hearts were frozen at 20 s, 30 s and 40 min after addition of noradrenaline and at 20 s and 40 min after addition of carbachol, and after 5 and 45 min of control perfusion. cAMP and cGMP were determined by radioligand methods and IP3 by a combined fast performance liquid chromatography (FPLC)-isotachophoretic method. cAMP increased by 36% within 20 s followed by a decrease (22%) during the 10 s following noradrenaline addition. After 40 min cAMP regained its value near that of 20 s. Noradrenaline perfusion did not influence IP3 levels during the first 30 s although the value at 40 min was significantly higher (59%). IP3 increased (42%) after 20 s of carbachol perfusion followed by a 25% decrease at 40 min. Sustained stimulation of beta-receptors (after 40 min in our model) resulted in a repeated increase in cAMP only, without an increase in contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anaesthesiology, University Hospital, Uppsala, Sweden.
authors.forename: H J
authors.initials: HJ
authors.lastname: Martinussen
authors.forename: A
authors.initials: A
authors.lastname: Waldenström
authors.forename: G
authors.initials: G
authors.lastname: Ronquist
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism*; D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013997:Time Factors
chemical_list: D011943:Receptors, Adrenergic, beta; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D000242:Cyclic AMP; D006152:Cyclic GMP; D009638:Norepinephrine