Fig. 3. Participation of the RyR in the [Ca²⁺]_i response to the ET_BR agonist IRL 1620 in shark mesenteric VSM. (A) Representative tracing of the diminished [Ca²⁺]_i response to IRL 1620 in the continued presence of the cADPR antagonist 8-Br cADPR. (B) Typical tracings of the stimulatory effect of a low concentration of ryanodine on the RyR and blocking effect of high concentrations of ryanodine. IRL 1620 was added in the continued presence of ryanodine. (C) Summary data of the response of VSM to a concentration of ryanodine that activates the RyR (5 µmol l^-1), followed by response to the ET_BR agonist IRL 1620 in the continued presence of ryanodine. The ryanodine and IRL 1620 plus ryanodine results were different from each other (^*P<0.05) and both were different from IRL 1620 alone (P<0.05). (D) Three inhibitors of the RyR, 8Br-cADPR, high concentration of ryanodine (100 µmol l^-1) and Ruthenium Red, block the response of VSM to the ET_BR agonist IRL 1620 by approximately 39% (^*P<0.01).