Inositolphosphate formation in thoracic and abdominal rat aorta following Gq/11-coupled receptor stimulation

Abstract

Although thoracic and abdominal rat aorta are often used as a classical pharmacological preparation for the assessment of vascular drug effects, little is known on regional differences among these two parts of the aorta with regard to their reaction to Gq/11-coupled receptor activation. Thus, we determined, in rings from thoracic and abdominal aorta from 12-week-old male Wistar rats, the effects of noradrenaline (NA; 10–8–10–4 M), endothelin-1 (ET-1; 10–10–10–6 M) and the thromboxane A2 mimetic U 46619 (10–8–10–5 M) on inositolphoshate (IP) formation (assessed as accumulation of total [3H]IPs in [3H]myo-inositol prelabelled rings). NA, ET-1 and U 46619 concentration-dependently increased IP formation; maximum increases were, however, significantly more pronounced in thoracic than in abdominal aorta. Similarly, NA, ET-1 and U 46619 evoked significantly larger maximum contractions in thoracic than in abdominal aorta. NA-induced [3H]IP formation could be inhibited with BMY 7378 (10–9–10–4 M) and with 5-methyl-urapidil (5-MU; 10–9–10–5 M) both exhibiting biphasic concentration-inhibition curves. The pK i-values for BMY 7378 at the high affinity site were in thoracic aorta 8.93±0.28 (n=5), and in abdominal aorta 8.76±0.35 (n=4) and at the low affinity site 6.45±0.2 (thoracic aorta) and 6.55±0.27 (abdominal aorta). pK i-Values for 5-MU in thoracic aorta at the high affinity site were 8.25±0.34 (n=4), and at the low affinity site 6.61±0.39 . In abdominal aorta reliable pK i-values could not be calculated for 5-MU due to a low signal-to-noise ratio. On the other hand, in both preparations the ETA-receptor antagonist BQ-123 (10–9–10–5 M) and the TP-receptor antagonist SQ 29548 (10–9–10–5 M) inhibited ET-1- and U 46619-induced IP formation, respectively, with monophasic concentration-inhibition curves: pK i-values for BQ-123 were: 8.16±0.24 (thoracic aorta) and 8.10±0.35 (abdominal aorta) and for SQ 29548: 8.2±0.3 (thoracic aorta) and 8.5±0.3 (abdominal aorta). The amount of immunodetectable Gq/11-protein was similar in both tissues. We conclude that responses to NA, ET-1 and U 46619 (IP formation and contractile force) are larger in thoracic than in abdominal aorta. ET-1 effects on IP formation are mediated by ETA-receptors and U 46619 effects by TP-receptors. NA effects are mediated by α1D- and α1A-adrenoceptors; α1B-adrenoceptors seem to play a minor role.

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