Comparison of the vasoconstrictor effects of rizatriptan and sumatriptan in human isolated cranial arteries: immunohistological demonstration of the involvement of 5-HT1B-receptors.
OBJECTIVE
We compared the vasoconstrictor effects of 5-HT with those of the selective 5-HT1B/1D-receptor agonists sumatriptan and rizatriptan in human isolated cranial (middle meningeal) arteries. In addition selective 5-HT1B- or 5-HT1D-receptor antibodies were used in combination with semiquantitative immunohistochemical techniques to compare the levels of expression of these receptors in human middle meningeal and coronary arteries.


METHODS
Middle meningeal and coronary arteries were obtained (with consent) from either neurosurgical patients or donor hearts, respectively. Segments of middle meningeal artery were mounted in organ baths for isometric recording and cumulative concentration-effect curves to 5-HT, rizatriptan and sumatriptan were obtained. Frozen fresh sections of middle meningeal and coronary arteries were subjected to standard immunohistochemical techniques using specific 5-HT1B- or 5-HT1D-receptor primary antibodies and a radiolabelled secondary antibody. Data were subjected to analysis of variance (ANOVA) and nonlinear regression analysis.


RESULTS
5-HT, rizatriptan and sumatriptan were potent vasoconstrictors in human isolated middle meningeal artery (EC50 values=32, 90 and 71 nM, respectively). A significantly higher level of 5-HT1B-receptor immunoreactivity was detected in middle meningeal artery compared with coronary artery (ANOVA, F=7.95, DF=1,4, P<0.05).


CONCLUSIONS
Rizatriptan and sumatriptan act selectively to cause vasoconstriction in human isolated middle meningeal artery and are 10-fold more potent than in human coronary artery. The higher level of expression of 5-HT1B-receptors in middle meningeal compared with coronary artery provides a pharmacological basis for the craniovascular selectively of both rizatriptan and sumatriptan.
Longmore
J
J
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Eastwick Road, Harlow, Essex, UK.
Razzaque
Z
Z
Shaw
D
D
Davenport
A P
AP
Maguire
J
J
Pickard
J D
JD
Schofield
W N
WN
Hill
R G
RG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003331:Coronary Vessels / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects*; D008875:Middle Aged; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000378:metabolism*; D018170:Sumatriptan / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D014363:Tryptamines; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D014230:Triazoles; D014363:Tryptamines; D014662:Vasoconstrictor Agents; C093622:rizatriptan; D018170:Sumatriptan