MODULATION OF NORADRENALINE RELEASE IN VIVO THROUGH PREJUNCTIONAL α‐ADRENOCEPTORS

Abstract

1. Extensive in vitro studies have suggested that noradrenaline release from sympathetic nerve endings is modulated by alpha 2-adrenoceptors on the terminal varicosities, activation of which by alpha-adrenoceptor agonists or neuronally released noradrenaline leads to inhibition of transmitter release. 2. Studies in intact animals support essentially the physiological operation of this mechanism, whereas human studies have reached mixed conclusions and more information is required.

Evidence that M1 muscarinic receptors enhance noradrenaline release in mouse atria by activating protein kinase C

“…This effect was found most likely to be due to activation of Ml muscarinic receptors at postganglionic sympathetic nerve varicosities (Costa & Majewski, 1991). One intraneuronal pathway involved in the enhancement of noradrenaline release from nerve terminals is the adenylate cyclase-cyclic AMP system (see Majewski et al, 1988). There have been reports that cyclic AMP levels in some neurones are raised following activation of muscarinic receptors (Hanley & Iversen, 1978;Lenox et al, 1980;Briggs et al, 1982), and a recent report indicates that muscarinic receptors in the rat olfactory bulb are linked directly to stimulation of adenylate cyclase activity (Onali & Olianas, 1990).…”

“…The aim of the present study was to characterize further the Ml facilitatory mechanism on sympathetic nerves by investigating the signal transduction pathway through which it operates. Candidate pathways include the adenosine 3':5'cyclic monophosphate (cyclic AMP) system since activation of this system results in enhanced release of noradrenaline (see Majewski et al, 1988); arachidonic acid metabolites since activation of muscarinic receptors releases arachidonic acid metabolites in many tissue and cell types (see Nathanson, 1987); and the phospholipase C pathway since in many systems Ml receptors transduce their effect through this system (see Fisher & Agranoff, 1987). Two important second messengers are formed as a result of phospholipase C activity; inositol trisphosphate and diacylglycerol (see Berridge, 1987).…”

The effect of adrenal demedullation on cardiovascular responses to environmental stimulation in conscious rats

“…Nevertheless, exposure to this environmental stimulus increases blood pressure acutely and has been shown to elevate plasma adrenaline levels and lead to the development of hypertension in rats (Rosecrans et al, 1966). Since adrenaline has been widely implicated in the facilitation of sympathetic activity (for review see: Majewski, 1983), it was of interest to ascertain the effects of adrenaline depletion on cardiovascular parameters and responses to alerting.…”