EFFECT OF ALPHA-ADRENERGIC AGONIST ON THE RABBIT EAR ARTERY CONTRACTION TO SEROTONIN - ENHANCED RESPONSE MEDIATED BY SEROTONERGIC(1-LIKE) RECEPTORS

The effect of methoxamine or phenylephrine (PHE) on the contractile re sponse of the rabbit ear artery to serotonin was assessed by using iso lated arterial rings mounted in tissue baths for the measurement of is ometric force development. A contractile threshold concentration of me thoxamine or PHE (10-30 nM) shifted the serotonin concentration-respon se curve to the left by approximately 200-fold. Neither mechanical rem oval of the vascular endothelium nor chemical denervation had any effe ct on the alpha agonist-amplified response of ear artery to serotonin. Although the response to serotonin in the absence of the alpha agonis t was mediated primarily by alpha-1 adrenergic receptors, prazosin did not block the amplified response to serotonin. Ketanserin (10 nM), ri tanserin (50 nM) and MDL 72222 (1 mu M) also had no effect on the ampl ified response, ruling out the involvement of serotonergic (5-HT)(2) a nd 5-HT3 receptors. However, methiothepin (3 nM) and 1-(1-naphthyl)pip erazine (10 and 100 nM) blocked the PHE-amplified contraction of ear a rtery to serotonin. When the contractile response of ear artery to 5-c arboxamidotryptamine was measured in the presence of a threshold conce ntration of alpha agonist, the concentration-response curve was shifte d 8300-fold to the left. The amplified response to 5-carboxamidotrypta mine was insensitive to 10 nM ketanserin, but was blocked by 3 nM meth iothepin. Sumatriptan, a selective 5-HT1 agonist, failed to induce vas oconstriction in the absence of a threshold concentration of alpha ago nist. However, in the presence of PHE, sumatriptan induced a concentra tion-dependent contraction. The rank order of potency of the 5-HT agon ists in the presence of the alpha agonist was 5-carboxamidotryptamine > serotonin > sumatriptan. It is concluded that the 5-HT receptor medi ating the alpha-amplified contraction of rabbit ear artery to serotoni n displays the pharmacological characteristics of 5-HT1-like receptors .