Effects of Drugs on the Accumulation and Spontaneous Release of Noradrenaline in the Rat Anococcygeus Muscle

Abstract

1The ability of drugs to inhibit noradrenaline accumulation and to release noradrenaline was studied in the isolated anococcygeus muscle of the rat. 2 Noradrenaline, tyramine, 2-amino,6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), 2-amino,6,7-dimethoxy-1,2,3,4-tetrahydronaphthalene (dimethyl ADTN), and 5-hydroxytryptamine were all potent inhibitors of noradrenaline accumulation and potent releasers of noradrenaline. ADTN was accumulated by the rat isolated anococcygeus muscle. 3 Amphetamine and desipramine were potent inhibitors of noradrenaline accumulation but poor releasers of noradrenaline. 4 Methoxamine, oxymetazoline, acetylcholine, and angiotensin were poor inhibitors of noradrenaline accumulation and did not release noradrenaline. 5 The mechanism of action of these drugs is discussed.

Facilitation of noradrenaline release from sympathetic nerves in rat anococcygeus muscle by activation of prejunctional β‐adrenoceptors and angiotensin receptors

“…These results suggest that the smooth muscle of rat anococcygeus also possesses angiotensin II receptors, as has been previously suggested (Doggrell & Woodruff, 1978), and provides further evidence for the local conversion of angiotensin I to angiotensin II in this tissue.…”

Cross-Talk Between AT1 and AT2Angiotensin Receptors in Rat Anococcygeus Smooth Muscle

“…Activation of the prejunctional receptor results in enhancement of norepinephrine (NE) release, which induces contractile response by activation of postjunctional ␣ 1 -adrenoceptors (Doggrell and Woodruff, 1978;James and Leighton, 1987;Li et al, 1988). The ultrastructure of nerve terminals in the rat anococcygeus muscle also offers support for a nonadrenergic, noncholinergic enervation of approximately 40% of the nerve terminals (Gibbins and Haller, 1979).…”

Effects of chronic antidepressant treatment on ?1- and ?2-adrenoceptors in the rat anococcygeus muscle

“…However, the treatment with mianserin and nomifensin, that are also inhibitors of noradrenaline uptake (Richelson and Pfenning, 1984) did not modify the sensitivity of the anococcygeus muscle to the a~-adrenoceptor agonist phenylephrine. One interpretation arises taking into account that the %-adrenoceptor antagonism of nomifensine and mianserin in the rat anococcygeus muscle (Doggrell and Woodruff, 1977;Ishida et al, 1988) could overcome the desensitization due to the increase of synaptic noradrenaline which results from inhibition of monoamine neuronal uptake while desipramine and nortryptiline did not. In contrast with our results long-term treatment with imipramine produces an increase of a~-adrenoceptor sensitivity in the anococcygeus muscle (Hong et al, 1986).…”

“…It is known that tricyclic antidepressants inhibit neuronal noradrenaline uptake not only in the central nervous system (Richelson and Pfenning, 1984) but also in peripheral tissues such as the anococcygeus muscle (Doggrell and Woodruff, 1977). Thus, chronic increase in the availability of noradrenaline at its receptors, could lead to a development of adrenoceptor subsensitivity.…”