Contributions of α1-adrenoceptors, α2-adrenoceptors and P2x-purinoceptors to neurotransmission in several rabbit isolated blood vessels: role of neuronal uptake and autofeedback

MacDonald, A., Daly, C.J. , Bulloch, J.M. and McGrath, J.C. (1992) Contributions of α1-adrenoceptors, α2-adrenoceptors and P2x-purinoceptors to neurotransmission in several rabbit isolated blood vessels: role of neuronal uptake and autofeedback. British Journal of Pharmacology, 105(2), pp. 347-354. (doi: 10.1111/j.1476-5381.1992.tb14257.x)

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Abstract

1. The roles of autofeedback and neuronal uptake in neurotransmission produced by electrical field stimulation in several rabbit isolated blood vessels were examined.<p></p> 2. Blocking drugs were used to separate the possible purinergic and noradrenergic contributions to the end organ response: prazosin, antagonist at postjunctional α1-adrenoceptors; rauwolscine and yohimbine, antagonists at pre- and postjunctional α<sub>2</sub>-adrenoceptors; α,β-methylene ATP, desensitizing agent at postjunctional P<sub>2x</sub>-purinoceptors. In addition to desensitizing postjunctional P<sub>2x</sub>-purinoceptors, α,β-methylene ATP potentiated the noradrenergic component of the nerve-induced responses.<p></p> 3. In the presence of an intact neuronal uptake mechanism, the vessels showed different contributions of purinergic (via P<sub>2x</sub>-purinoceptors) and noradrenergic (via α<sub>1</sub>-adrenoceptors and α2-adrenoceptors) components to the end organ response to nerve stimulation: saphenous artery (approximately equal contributions from P<sub>2x</sub>-purinoceptors and α<sub>1</sub>-adrenoceptors), ileocolic artery (mainly P<sub>2x</sub>-purinoceptors with a smaller contribution from α<sub>1</sub>-adrenoceptors), plantaris vein (mainly α<sub>1</sub>-adrenoceptors with a small contribution from α<sub>2</sub>-adrenoceptors and P<sub>2x</sub>-purinoceptors) and saphenous vein (α<sub>1</sub>-adrenoceptors).<p></p> 4. The presence of α<sub>2</sub>-adrenoceptor-mediated autofeedback could be demonstrated for both purinergic and noradrenergic components of the nerve-induced responses in the artery preparations. In the veins, potentiation of nerve-induced responses by α<sub>2</sub>-adrenoceptor antagonists could not be studied due to blockade of postjunctional α<sub>2</sub>-adrenoceptor-mediated vasoconstriction.<p></p> 5. Blockade of neuronal uptake with cocaine potentiated the noradrenergic component of the nerve-induced responses. Both α<sub>1</sub>-adrenoceptor- and α<sub>2</sub>-adrenoceptor-mediated components were potentiated, with a relatively greater potentiation of the α<sub>2</sub>-adrenoceptor-mediated component. In the case of saphenous vein an α<sub>2</sub>-adrenoceptor-mediated component which was previously absent was uncovered.<p></p> 6. Blockade of neuronal uptake with cocaine had no effect or reduced the purinergic component of responses, the latter effect presumably due to enhanced α<sub>2</sub>-adrenoceptor-mediated autofeedback..<p></p> 7. In the presence of cocaine, nerve-induced responses in the saphenous vein were biphasic. Rauwolscine potentiated the first phase and inhibited the second phase thus demonstrating effects of pre- and postjunctional α<sub>2</sub>-adrenoceptor-mediated activation in the same preparation.<p></p> 8. In conclusion, neuronal uptake and autofeedback processes play important and complex interacting parts in determining the relative contributions of α<sub>1</sub> and α<sub>2</sub>-adrenoceptors and P<sub>2x</sub>-purinoceptors in the end organ response to neurotransmission in blood vessels.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McGrath, Professor John and Daly, Professor Craig
Authors: MacDonald, A., Daly, C.J., Bulloch, J.M., and McGrath, J.C.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:British Journal of Pharmacology
Publisher:John Wiley & Sons, Inc.
ISSN:0007-1188
ISSN (Online):1476-5381

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