THE 5-HT1-LIKE RECEPTORS MEDIATING INHIBITION OF SYMPATHETIC VASOPRESSOR OUTFLOW IN THE PITHED RAT - OPERATIONAL CORRELATION WITH THE 5-HT1A, 5-HT1B AND 5-HT1D SUBTYPES

1 It has been suggested that the inhibition of sympathetically-induced vasopressor responses produced by 5-hydroxytryptamine (5-MT) in pithe d rats is mediated by 5-HT1-like receptors. The present study has re-a nalysed this suggestion with regard to the classification schemes rece ntly proposed by the NC-IUPHAR subcommittee on 5-HT receptors. 2 Intra venous (i.v.) continuous infusions of 5-HT and the 5-HT1 receptor agon ists, 8-OH-DPAT (5-HT1A), indorenate (5-HT1A), CP 93,129 (5-HT1B) and sumatriptan (5-HT1B/1D), resulted in a dose-dependent inhibition of sy mpathetically-induced vasopressor responses. 3 The sympatho-inhibitory responses induced by 5-MT, 8-OH-DPAT, indorenate, CP 93,129 or sumatr iptan were analysed before and after i.v. treatment with blocking dose s of the putative 5-HT receptor antagonists, WAY 100635 (5-HT1A), cyan opindolol (5-HT1A/1B) or GR 127935 (5-HT1B/1D). Thus, after WAY 100635 , the responses to 5-HT and indorenate, but not to 8-OH-DPAT, CP 93,12 9 and sumatriptan, were blocked. After cyanopindolol, the responses to 5-MT, indorenate and CP 93,129 were abolished, whilst those to 8-OH-D PAT and sumatriptan (except at the lowest frequency of stimulation) re mained unaltered. In contrast, after GR 127935, the responses to 5-MT, CP 93,129 and sumatriptan, but not to 8-OH-DPAT and indorenate, were abolished. 4 In additional experiments, the inhibition induced by 5-HT was not modified after 5-HT7 receptor blocking doses of mesulergine. 5 The above results suggest that the 5-HT1-like receptors, which inhib it the sympathetic vasopressor outflow in pithed rats, display the pha rmacological profile of the 5-HT1A, 5-HT1B and 5-MT1D, but not that of 5-HT7, receptors.