Cardiac binding of [3H]inositol 1,4,5-trisphosphate following chronic stimulation of cyclic AMP signalling in guinea pigs.
Binding of [3H]inositol 1,4,5-trisphosphate ([3H]IP3) to guinea pig heart has been characterised, localised and the effect of the in vivo desensitisation of cardiac beta-adrenoceptorcyclic AMP signalling examined. Quantitative autoradiography showed highest levels of [3H]IP3 binding associated with coronary blood vessels and with the endothelial cells of the aorta and the mitral and tricuspid valves. Moderate levels of [3H]IP3 bound to the atrioventricular conducting system, cardiac valves and aortic smooth muscle. Lower levels of [3H]IP3 binding were detected in atrial and ventricular myocardium. Although the phosphoinositide signalling pathway does not contribute greatly to normal cardiac function, there is evidence of an increased importance in situations of compromised excitation-contraction such as occurs in cardiac failure or with, beta-adrenoceptor desensitisation. We examined whether chronic in vivo stimulation of beta-adrenoceptor-adenylate cyclase signalling affected cardiac binding of [3H]IP3. Infusion of guinea pigs with isoprenaline (400 micrograms kg-1 h-1, 7 days) tended to reduce [3H]IP3 binding in myocardium although not significantly (P > 0.05, n = 4). These data indicate that [3H]IP3 binding has a heterogeneous distribution in guinea pig heart with highest levels of binding discretely localised to endothelial cells. Desensitisation of beta-adrenoceptor-cyclic AMP signalling in heart did not lead to upregulation of [3H]IP3 binding.
McMartin
L
L
Prince Henry's Institute of Medical Research, Monash Medical Centre, Clayton, Australia.
Summers
R J
RJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D013268:Stimulation, Chemical; D014316:Tritium
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D014316:Tritium; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D007545:Isoproterenol