NONADRENERGIC CONTRACTILE RESPONSE OF GUINEA-PIG PORTAL-VEIN TO ELECTRICAL-FIELD STIMULATION MIMICS RESPONSE TO UTP BUT NOT TO ATP

Transmural electrical field stimulation (EFS, 4-32 Hz) produced a biph asic contractile response consisting of a rapid and transient contract ion (first phase) followed by a slow contraction (second phase) in rin g preparations of guinea pig portal veins. Both contractions were enha nced by the nitric oxide synthase inhibitor N-G-nitro-L-arginine methy l ester (L-NAME, 30 mu M). In the presence of L-NAME, tetrodotoxin (1 mu M) and guanethidine (3 mu M) inhibited both contractions and phento lamine (10 mu M), and reserpine treatment abolished the first-phase co ntraction without affecting the second-phase contraction. These result s suggest that the first-phase contraction is caused by norepinephrine released from the perivascular nerves. In the presence of phentolamin e and L-NAME, the second-phase contraction was inhibited by the nonsel ective P-2-purinoceptor antagonist suramin (30-300 mu M) and the P-2y- purinoceptor antagonist reactive blue 2 (RB2; 10-100 mu M). alpha,beta -Methylene-adenosine triphosphate (alpha,beta-mATP; 3-30 mu M), which desensitizes P-2x-purinoceptors, and the P-2x-purinoceptor antagonist 4,4'-diisothiocyanatostilbene-2,2'-disulphonate (DIDS; 1-10 mu M) had a little effect. Exogenous ATP (0.1-3 mM) and UTP (0.1-3 mM) in the pr esence of L-NAME produced contractions in a concentration-dependent ma nner. The ATP-induced contraction was enhanced by suramin, RB2, and DI DS but unaltered by alpha,beta-mATP. The UTP-induced contraction was i nhibited by suramin and RB2 but unaltered by alpha,beta-mATP and DIDS. These results indicate that in the guinea pig portal vein, the classi c P-2x-purinoceptors do not contribute to the nonadrenergic component of sympathetic neurotransmission. Furthermore, the pharmacology of the nonadrenergic component of neurotransmission resembles that of vasoco nstrictor responses to exogenous UTP rather than to ATP.