5-HT1-like receptor mediated changes in porcine carotid haemodynamics: are 5-HT1D receptors involved?

5-Hydroxytryptamine (5-HT) reduces porcine arteriovenous shunting in the carotid vascular bed by stimulation of both 5-HT1-like and 5-HT2 receptors and increases capillary flow to some tissues, like the skin and ears, by different 5-HT1-like receptors. In view of the heterogeneous nature of the 5-HT1-like receptors and the relative selectivity for the 5-HT1D binding sites of sumatriptan, which also reduces porcine arteriovenous shunting and slightly increases capillary blood flow towards skin and ears by 5-HT1-like receptors, we have attempted to determine whether one or both of these carotid 5-HT1-like receptors belong to the 5-HTID subtype. Pentobarbitone anaesthetized pigs, subjected to bilateral cervical vagosympathectomy, received either 5-HT (2 μg · kg-1 · min-1) in the carotid artery or cumulative i.v. doses of sumatriptan (10, 30, 100 and 300 μg · kg-1). Their effect on the total carotid blood flow and its distribution into capillary and arteriovenous anastomotic parts was determined with radioactive microspheres. The effect of metergoline (1 mg·kg-1), a substance with a very high affinity for the 5-HT1D receptor as well as for the 5-HT1A, 5-HT1B, 5-HT1C and 5-HT2 receptors, was studied on the responses to 5-HT and sumatriptan. Both 5-HT and sumatriptan reduced carotid arteriovenous anastomotic blood flow. 5-HT and, to a lesser extent, sumatriptan also increased capillary blood flow towards some tissues. Metergoline by itself did not affect the distribution of porcine carotid blood flow. It attenuated the constrictor response, but increased the vasodilator response to 5-HT, in a manner similar to the 5-HT2 receptor antagonists cyproheptadine, ketanserin and WAL 1307 in our former experiments. These effects seem, therefore, to be related to the blockade of 5-HT2 receptors by metergoline. On the other hand, metergoline had no significant effect against the responses to sumatriptan. It is concluded that neither the constrictor nor the dilator carotid 5-HT1-like receptors seem to be related to the known 5-HT1 binding subtypes, including the 5-HT1D subtype.

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