The 5-HT1-like receptor mediating reduction of porcine carotid arteriovenous shunting by RU 24969 is not related to either the 5-HT1A or the 5-HT1B subtype.
Using the radioactive microsphere technique in anaesthetized pigs, we studied the systemic and carotid haemodynamic effects of intracarotid infusions (0.3, 1, 3 and 10 micrograms/kg.min) of 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969), a drug with high affinity for 5-HT1A and 5-HT1B recognition sites. Unlike in the rat, RU 24969 did not elicit hypotension in the pig. Instead, the two highest doses of the drug caused a slight increase in blood pressure. RU 24969 reduced common carotid artery blood flow by decreasing the non-nutrient, arteriovenous anastomotic blood flow; the nutrient, arteriolar blood flow was mildly increased. The decrease in common carotid and arteriovenous anastomotic blood flow was only slightly attenuated in animals pretreated with the 5-HT2 receptor antagonist, ketanserin (0.5 mg/kg i.a.), but was markedly reduced in animals pretreated with the 5-HT1-like and 5-HT2 receptor antagonist, methiothepin (1.0 mg/kg i.a.). However, these responses were not modified after pretreatment with the putative 5-HT1A and 5-HT1B receptor antagonist, (+/-)-pindolol (4.0 mg/kg i.v.). The slight increase in arteriolar blood flow was attenuated in the animals pretreated with either ketanserin, methiothepin or (+/-)-pindolol. It is concluded that the RU 24969-induced reduction in common carotid and arteriovenous anastomotic blood flow is mediated mainly by 5-HT1-like receptors, which do not seem to correspond to either the 5-HT1A or 5-HT1B receptor subtypes.
Bom
A H
AH
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Villalón
C M
CM
Verdouw
P D
PD
Saxena
P R
PR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D007650:Ketanserin / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D008863:Microspheres; D010869:Pindolol / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D013552:Swine
D007211:Indoles; D011985:Receptors, Serotonin; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D008719:Methiothepin; D007650:Ketanserin; D010869:Pindolol