Adenosine modulates alpha2-adrenergic receptors within specific subnuclei of the nucleus tractus solitarius in normotensive and spontaneously hypertensive rats.
Adenosine is known to modulate neuronal activity within the nucleus tractus solitarius (NTS). The modulatory effect of adenosine A1 receptors (A1R) on alpha2-adrenoceptors (Adr2R) was evaluated using quantitative radioautography within NTS subnuclei and using neuronal culture of normotensive (WKY) and spontaneously hypertensive rats (SHR). Radioautography was used in a saturation experiment to measure Adr2R binding parameters (Bmax, Kd) in the presence of 3 different concentrations of N6-cyclopentyladenosine (CPA), an A1R agonist. Neuronal culture confirmed our radioautographic results. [3H]RX821002, an Adr2R antagonist, was used as a ligand for both approaches. The dorsomedial/dorsolateral subnucleus of WKY showed an increase in Bmax values (21%) induced by 10 nmol/L of CPA. However, the subpostremal subnucleus showed a decrease in Kd values (24%) induced by 10 nmol/L of CPA. SHR showed the same pattern of changes as WKY within the same subnuclei; however, the modulatory effect of CPA was induced by 1 nmol/L (increased Bmax, 17%; decreased Kd, 26%). Cell culture confirmed these results, because 10(-5) and 10(-7) mol/L of CPA promoted an increase in [3H]RX821002 binding of WKY (53%) and SHR cells (48%), respectively. DPCPX, an A1R antagonist, was used to block the modulatory effect promoted by CPA with respect to Adr2R binding. In conclusion, our study shows for the first time an interaction between A1R that increases the binding of Adr2R within specific subnuclei of the NTS. This may be important in understanding the complex autonomic response induced by adenosine within the NTS. In addition, changes in interactions between receptors might be relevant to understanding the development of hypertension.
Carrettiero
Daniel C
DC
Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
Almeida
Renato S
RS
Fior-Chadi
Debora R
DR
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D042581:Intranuclear Space / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism*; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D018341:Receptors, Adrenergic, alpha-2; D014970:Xanthines; C048599:N(6)-cyclopentyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine