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.
1. The interaction between alpha(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(-11) - 10(-7) M), angiotensin III (10(-10) - 10(-6) M) and bradykinin (10(-11) - 10(-7) M) enhanced the evoked overflow of tritium when preparations were stimulated with conditions that led to marked alpha(2)-autoinhibition (120 pulses at 3 Hz), but not when stimulated with conditions that led to little alpha(2)-autoinhibition (20 pulses at 50 Hz). 3. Blockade of alpha-adrenoceptors by phentolamine (1 or 10 microM) reduced or abolished the effect of angiotensin II and bradykinin on the overflow response to 120 pulses at 3 Hz. 4. Addition of the delta-opioid agonist [D-Ser(2)]-leucine enkephalin-Thr (DSLET, 0.1 microM), or of neuropeptide Y (0.1 microM), together with phentolamine, restored the effect of angiotensin II and bradykinin. 5. The beta-adrenoceptor agonist terbutaline (10(-9) - 10(-4) M) enhanced the evoked overflow of tritium irrespective of the degree of autoinhibition. 6. The experiments show that (i) a marked prejunctional facilitatory effect of angiotensin and bradykinin in mouse isolated atria requires prejunctional alpha(2)-autoinhibition; (ii) in the absence of alpha(2)-autoinhibition, activation of other prejunctional G(i/o) protein-coupled receptors, namely opioid and neuropeptide Y receptors, restores a marked effect of angiotensin II and bradykinin; and (iii) the facilitatory effect of terbutaline is not dependent upon the degree of alpha(2)-autoinhibition. The findings indicate that the major part of the release-enhancing effect elicited through prejunctional G(q/11) protein-coupled receptors is due to disruption of an ongoing, alpha(2)-autoreceptor-triggered G(i/o) protein mediated inhibition.
Cox
S L
SL
Pharmakologisches Institut, Universität Freiburg, Hermann-Herder-Strasse 5, D-79104, Freiburg i. Br., Germany. scox@prontomail.com
Schelb
V
V
Trendelenburg
A U
AU
Starke
K
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000805:Angiotensin III / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D020239:Receptor Cross-Talk / Q000187:drug effects*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D011945:Receptors, Angiotensin / Q000187:drug effects; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D009478:Neuropeptide Y; D018341:Receptors, Adrenergic, alpha-2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000805:Angiotensin III; D004743:Enkephalin, Leucine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D019204:GTP-Binding Proteins; D013726:Terbutaline; D001920:Bradykinin; D002118:Calcium; D009638:Norepinephrine