Erlij showed that adenosine stimulates the secretion of chloride by the rectal gland of Squalus acanthias, with an order of potency of NECA > Adenosine > PIA. This effect is mediated by an A2a receptor, as evidenced by the tests using adenosine analogs. In addition, adenosine increases cyclic AMP levels in the gland. However, adenosine does not circulate at the concentrations needed to stimulate secretion. Adenosine is released from rectal gland cells after activation of secretion. At micromolar concentrations adenosine inhibits the secretion by the gland stimulated by different secretagogues. The effect of adenosine appears to be mediated by an A1 receptor that was cloned and labeled an A0 receptor. ATP is also released from the gland after stimulation and also inhibits the stimulated secretion of chloride by the gland at micromolar concentrations through a yet unknown receptor. Therefore purines, both adenosine and ATP, appear to exert a feedback regulation on the secretion of chloride by the shark rectal gland. When the secretion of chloride is activated or stimulated, both adenosine and ATP are released from the rectal gland cells and exert an inhibitory check on its secretion.