Interaction between angiotensin II and glucose sensing at the subfornical organ.

ABSTRACT

The subfornical organ (SFO) lacks the normal blood-brain barrier and senses the concentrations of many different circulating signals, including glucose and angiotensin II (ANG II). ANG II has recently been implicated in the control of food intake and body weight gain. The present study assessed whether single SFO neurones sense changes in glucose and ANG II, and also whether changes in glucose concentration alter the responsiveness of these neurones to ANG II. SFO neurones dissociated from male Sprague-Dawley rats (100-175 g) were used. We first examined whether glucose concentration modulates AT1 receptor expression. Similar AT1a mRNA expression levels were found at glucose concentrations of 1, 5 and 10 mmol L-1 in dissociated SFO neurones. Glucose responsiveness of SFO neurones was assessed using perforated current-clamp recordings and switching between 5 and 10 mmol L-1 glucose artificial cerebrospinal fluid to classify single neurones as nonresponsive (nGS), glucose-excited (GE) or glucose-inhibited (GI). In total, 26.7% of the SFO neurones were GI (n = 24 of 90), 21.1% were GE (n = 19 of 90) and 52.2% were nGS (n = 47 of 90). Once classified, the effects of 10 nmol L-1 ANG II on the excitability of these neurones were tested, with 52% of GE (n = 10 of 19), 71% of GI (n = 17 of 24) and 43% of nGS (n = 20 of 47) neurones being ANG II sensitive. Finally, we tested whether acute changes in glucose concentration modified the response to ANG II and showed that some neurones (4/17) only respond to ANG II at 10 mmol L-1 glucose. Our data demonstrate that the same SFO neurone can sense glucose and ANG II and that acute changes in glucose concentration may change ANG II responsiveness.