Enhancement of noradrenaline release by angiotensin II and bradykinin in mouse atria: evidence for cross‐talk between G_q/11 protein‐ and G_i/o protein‐coupled receptors

Abstract

1 The interaction between a 2 -autoreceptors and receptors for angiotensin (AT 1 ) and bradykinin (B 2 ) was studied in mouse isolated atria. The preparations were labelled with [ 3 H]-noradrenaline and then superfused with desipramine-containing medium and stimulated electrically. 2 Angiotensin II (10 711 ± 10 77 M), angiotensin III (10 710 ± 10 76 M) and bradykinin (10 711 ± 10 77 M) enhanced the evoked over¯ow of tritium when preparations were stimulated with conditions that led to marked a 2 -autoinhibition (120 pulses at 3 Hz), but not when stimulated with conditions that led to little a 2 -autoinhibition (20 pulses at 50 Hz). 3 Blockade of a-adrenoceptors by phentolamine (1 or 10 mM) reduced or abolished the e ect of angiotensin II and bradykinin on the over¯ow response to 120 pulses at 3 Hz. 6 The experiments show that (i) a marked prejunctional facilitatory e ect of angiotensin and bradykinin in mouse isolated atria requires prejunctional a 2 -autoinhibition; (ii) in the absence of a 2 -autoinhibition, activation of other prejunctional G i/o protein-coupled reeptors, namely opioid and neuropeptide Y receptors, restores a marked e ect of angiotensin II and bradykinin; and (iii) the facilitatory e ect of terbutaline is not dependent upon the degree of a 2 -autoinhibition. The ®ndings indicate that the major part of the release-enhancing e ect elicited through prejunctional G q/11 protein-coupled receptors is due to disruption of an ongoing, a 2 -autoreceptor-triggered G i/o protein mediated inhibition.

Adenosine A2A receptor‐mediated facilitation of noradrenaline release involves protein kinase C activation and attenuation of presynaptic inhibitory receptor‐mediated effects in the rat vas deferens

“…In preparations where interactions between adenosine A 1 and A 2A receptors have been observed, adenosine A 2A receptor-mediated effects were prevented by inhibition of protein kinase C (Dixon et al 1997;Lopes et al 1999, Cunha andRibeiro 2000a,b;Lopes et al 2002). Similar interactions, involving a 2 -adrenoceptors and angiotensin AT1 or bradykinin B2 receptors, which are coupled to the G q -phospholipase C-protein kinase C pathway, have also been described in mouse peripheral tissues (Cox et al 2000).…”

Angiotensin AT1 – α2C-Adrenoceptor Interaction Disturbs α2A-auto-Inhibition of Catecholamine Release in Hypertensive Rats

“…AT 1 R-G q -signaling stimulates norepinephrine release by interfering with the down-stream signaling of G i (Cox et al, 2000). The AT 1 R/α 2 AR interaction involved only the α 2C - and not the α 2A -subtype (Trendelenburg et al, 2003a).…”

Angiotensin II Induces Catecholamine Release by Direct Ganglionic Excitation

“…6 Such facilitation of norepinephrine (NE) release has frequently been investigated in isolated tissues under electrical stimulation 7,8 and appears to depend on a presynaptic autoinhibitory tone that is relieved in response to ANG. 9,10 The inability of ANG to induce catecholamine release from isolated tissues in the absence of electrical excitation 6,7,11 provoked the common view that facilitation of depolarization-induced catecholamine release represents the essential interaction of ANG with the peripheral sympathetic system in intact animals as well.…”