RTN TRH causes prolonged respiratory stimulation

We injected thyrotropin-releasing hormone (TRH; 10 nl; 0.25, 0.5, 1.0, or 10 mM), its inactive free acid form (TRHOH; 1 mM), or a metabolite with low TRH-receptor binding affinity, histidine-proline diketopiperazine (cHP; 1 mM), into the retrotrapezoid nucleus of anesthetized rats. Injection location was verified by anatomic analysis. Lower doses (0.25-0.5 mM) significantly increased both the product of integrated phrenic amplitude and frequency (integral Phr.f) and f for 20-30 min compared with artificial cerebrospinal fluid control injections. Higher doses (1.0-10 mM) produced greater and long-lasting stimulation of integral Phr.f, integral Phr, and f and of blood pressure. This stimulation reached values 150% of baseline and durations of 270 min after a single injection. TRHOH (1 mM) or cHP (1 mM) had no effect on integral Phr but increased f, as did 1 mM TRH. We conclude that TRH has a very powerful stimulatory effect in the retrotrapezoid nucleus region on integral Phr.f, with the integral Phr response seemingly specific for TRH receptors. Similar responses of f to TRHOH and cHP suggest it may be nonspecific.