Inositol-1,4,5-trisphosphate mass content in isolated perfused rat heart during alpha-1-adrenoceptor stimulation.
Inositol-1,4,5-trisphosphate (IP3) has been proposed to be a second messenger in response to alpha-1-adrenoceptor stimulation also in myocardial cells. We studied the effect of alpha-1-adrenoceptor stimulation (5 x 10(-5) mol/l phenylephrine or 5 x 10(-5) mol/l noradrenaline both in the presence of 10(-6) mol/l timolol) on IP3 mass content in isolated perfused rat hearts. IP3 content was determined by a specific receptor-binding assay-kit (TRK 1000, Amersham) after validating the method. For comparison also the effect of muscarinic stimulation (10(-4) mol/l carbachol in the presence of 10(-6) mol/l timolol) on IP3 content was measured in corresponding preparations. A basal IP3 level of about 75 pmol/mg protein was found. There were no prominent effects of alpha-1-adrenoceptor stimulation on total IP3 content in isolated perfused rat hearts. Phenylephrine gave a statistically significant increase of about 40% at 1/4 min and a statistically significant decrease of about 25% at 4 min after start of exposure. Noradrenaline, however, gave no statistically significant change of IP3 at the time-points studied. Muscarinic stimulation caused a slight, statistically insignificant, increase of IP3 at 1/4 min. The results are compatible with an assumption that agonist stimulation evokes a localized increase of IP3 which may be masked by a relatively high total IP3 mass content. The IP3 peak after phenylephrine coincided with the early positive inotropic phase of the response reported earlier in perfused rat hearts for alpha-1-adrenoceptor stimulation by phenylephrine. Although this might be compatible with a role for IP3 in this early and transient phase, a mediator function of IP3 in the inotropic response is not established.
Hanem
S
S
Department of Pharmacology, University of Oslo, Norway.
Enger
M
M
Skomedal
T
T
Osnes
J B
JB
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D009638:Norepinephrine