Effects of prostaglandin I2 and carbocyclic thromboxane A2 on smooth muscle cells and neuromuscular transmission in the guinea-pig mesenteric artery.
1 In the guinea-pig mesenteric arteries neither prostacyclin (PGI(2)) nor carbocyclic thromboxane A(2) (cTxA(2)) affected membrane potential in concentrations below 1 x 10(-6) M. Increasing the concentration to 3 x 10(-6) M either slightly hyperpolarized or depolarized the membrane with little change in membrane resistance.2 At a concentration of 1 x 10(-7) M, the amplitude of the first e.j.p. and the enlarged amplitudes of the subsequent e.j.ps evoked by trains of stimuli were reduced consistently by PGI(2) or cTxA(2). Facilitation was unaffected by either agent.3 The inhibitory actions of PGI(2) were partly overcome by increased concentrations of 5 mM [Ca](o) and were accelerated by a reduced concentration of 1.25 mM [Ca](o).4 The amplitude of the contraction evoked by perivascular nerve stimulation was inhibited to a greater extent by PGI(2) than by cTxA(2) at concentrations below 1 x 10(-6) M.5 The contraction evoked by 5 x 10(-6) M noradrenaline (NA) or excess concentrations of 20.2 mM [K](o) was enhanced by 1 x 10(-8) M - 1 x 10(-6) M cTxA(2) and suppressed by 1 x 10(-8) M - 1 x 10(-6) M PGI(2). The minimum concentration of cTxA(2) required to produce the contraction was 1 x 10(-8) M.6 These results indicate that transmission at the neuromuscular junction was inhibited consistently by PGI(2) or cTxA(2), presumably due to inhibition of NA release by suppression of the Ca influx at the nerve terminals. Whereas PGI(2) inhibited, cTxA(2) enhanced the mechanical response by a direct action on the smooth muscle cells.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D011464:Epoprostenol / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D013931:Thromboxanes / Q000494:pharmacology*
D011453:Prostaglandins; D011942:Receptors, Adrenergic, alpha; D013931:Thromboxanes; C024587:thromboxane A2, carbocyclic; D013928:Thromboxane A2; D011464:Epoprostenol; D002118:Calcium; D009638:Norepinephrine