COMPARISON OF SEROTONIN WITH DIRECTLY AND INDIRECTLY ACTING COMPOUNDS IN THEIR EFFECT ON THE NICTITATING MEMBRANE OF SPINAL CATS

¹ Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts

The action of serotonin and some related compounds (intracarotid administration) was studied on the acutely and chronically denervated nictitating membrane of spinal cats. Doseresponse curves have been established for the directly acting compounds serotonin, norepinephrine and acetylcholine and for the indirectly acting compounds tyramine and nicotine and for tryptamine. Norepinephrine and acetylcholine produced almost equivalent contractions of the acutely denervated nictitating membrane. Serotonin was found to be one-sixth as effective as norepinephrine. However, the contractions were of considerably longer duration than the ones induced with the former two drugs. Tryptamine was one-twentieth as effective as norepinephrine. Chronic denervation increased the sensitivity to norepinephrine, serotonin and acetylcholine 125, 50 and 25 times, respectively, as compared with the acutely denervated nictitating membrane. A small dose of atropine selectively blocked in the acutely denervated membrane the contraction induced by intracarotid injection of acetylcholine. Phentolamine predominantly inhibited the effect of norepinephrine and, to a lesser degree, of serotonin. These latter observations suggest that the three directly acting compounds activate the smooth muscle of the nictitating membrane at different receptor sites. On the acutely denervated preparations previous injections of serotonin increased the effect of subsequent injection of serotonin, norepinephrine or acetylcholine.