ENDOTHELIN RECEPTORS MEDIATING CONTRACTION IN GOAT CEREBRAL-ARTERIES

1 The aim of the present study was to identify the subtype of receptor mediating contraction to endothelin-1 and sarafotoxin S6b in goat iso lated middle cerebral arteries. 2 Endothelin-1, endothelin-2 and endot helin-3 contracted cerebral arteries in a concentration-dependent mann er. Although the three peptides were full agonists. the order of poten cy was endothelin-1 = endothelin-2 > endothelin-3, with a relative pot ency of endothelin- 1 and endothelin-2 versus endothelin-3 of approxim ately 280. Sarafotoxin S6b induced concentration-dependent contraction s with lower potency than endothelin-1/endothelin-2, higher potency th an endothelin-3 and a higher maximum response than the three endotheli ns. 3 The selective ETA-receptor antagonist, BQ-123, did not induce ch anges in either the resting tension or in the active tone developed by depolarization. In contrast, BQ-123 produced concentration-dependent relaxations of endothelin-1-precontracted cerebral arteries, and to a greater extent of sarafotoxin S6b-precontracted arteries. 4 Concentrat ion-response curves to endothelin-1 and sarafotoxin S6b were competiti vely antagonized by BQ-123 (pA2 of 7.43 +/- 0.12 and 8.41 +/- 0.09, re spectively). In contrast, BQ-123 had no effect on 5-hydroxytryptamine- elicited contractions even at 10(-6) M. 5 It is concluded that both th e order of potency of endothelin isopeptides and the antagonism of BQ- 123 point to the existence of ET(A) receptors mediating vasoconstricti on to endothelin-I and sarafotoxin S6b in the goat middle cerebral art ery. The different antagonistic potency of BQ-123 against endothelin-1 and sarafotoxin S6b suggests the existence of subtypes of ET(A) recep tors.