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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2001-03, Vol.363 (3), p.322-329
• Main Authors: Dhein, S, Giessler, C, Becker, K, Pönicke, K, Brodde, O E
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Aorta, Abdominal - drug effects; Aorta, Abdominal - metabolism; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Clonidine - analogs & derivatives; Clonidine - pharmacology; Endothelin Receptor Antagonists; Endothelin-1 - pharmacology; GTP-Binding Protein alpha Subunits, Gq-G11; Heterotrimeric GTP-Binding Proteins - metabolism; Heterotrimeric GTP-Binding Proteins - physiology; In Vitro Techniques; Inositol Phosphates - biosynthesis; Male; Muscle Contraction - drug effects; Norepinephrine - pharmacology; Peptides, Cyclic - pharmacology; Piperazines - pharmacology; Rats; Rats, Wistar; Receptor, Endothelin A; Receptors, Adrenergic, alpha - metabolism; Receptors, Adrenergic, alpha - physiology; Receptors, Endothelin - metabolism; Receptors, Endothelin - physiology; Receptors, Thromboxane - metabolism; Receptors, Thromboxane - physiology; Vasoconstrictor Agents - pharmacology
• ISSN: 0028-1298
• DOI: 10.1007/s002100000344

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]myoinositol 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 pKi-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). pKi-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 pKi-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: pKi-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 alpha1D- and alpha1A-adrenoceptors; alpha1B-adrenoceptors seem to play a minor role.