PURINERGIC RECEPTORS IN THE NUCLEUS-TRACTUS-SOLITARIUS MEDIATE DISTINCT CARDIORESPIRATORY RESPONSE PATTERNS

The purpose of the study was to examine the role of brainstem purinergic receptors in mechanisms of cardiorespiratory control mediated by the nucleus tractus solitarius (NTS), the major integrative site in the brainstem involved in the regulation of cardiorespiratory function and the reflex coordination of cardiorespiratory response patterns. Microinjections of selective agonists for purinergic receptor subtypes were made into the caudal NTS of anesthetized, spontaneous breathing rats. CGS 21680, a selective agonist for adenosine A2a receptors, elicited pronounced, dose-related decreases in blood pressure, whereas cyclopentyladenosine (CPA), a selective agonist at adenosine A1 receptors, elicited dose-related increases in blood pressure. These depressor and pressor response patterns were completely and selectively blocked, respectively, by pretreatment with CGS 15943A, a selective A2a receptor antagonist, and by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) a selective A1 receptor antagonist. 5'-N-ethylcarboxamidoadenosine (NECA), an analog exhibiting mixed agonist actions at adenosine receptor subtypes, elicited both depressor and pressor responses depending on the dosage. Additionally, in contrast to the findings with CGS 21680 and CPA, only NECA elicited very pronounced, dose-related decreases in respiratory rate at dosages which did not affect blood pressure. Related lines of evidence suggested that NECA-induced depression of respiration was mediated via A2b receptors. Microinjections of alpha,beta-MeATP, a selective agonist for P2x receptors, elicited apnea, and these effects were blocked by suramin, a selective antagonist at P2x receptors, but not by DMPX, a methylxanthine exhibiting mixed antagonist properties at P1 adenosine receptors. Moreover, similar microinjections of 2-MeSATP, a selective agonist at P2x receptors, were ineffective in eliciting cardiorespiratory responses even at 50-fold higher dosages. These results indicate that selective in vivo activation of purinergic receptors in the NTS may elicit distinct cardiorespiratory response patterns and it is likely that brainstem purinergic receptors may therefore play a crucial role under both physiologic and pathophysiologic conditions.