Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a series of triptans we characterized in vitro the 5-hydroxytryptamine (5-HT) receptor that mediates the contraction in guinea-pig iliac arteries moderately precontracted by prostaglandin F2alpha (PGF2alpha). Additionally, we investigated by reverse-transcriptase polymerase chain reaction (RT-PCR) which triptan-sensitive receptor is present in this tissue. Frovatriptan, zolmitriptan, rizatriptan, naratriptan, sumatriptan, and almotriptan contracted guinea-pig iliac arteries with pD2 values of 7.52+/-0.04, 6.72+/-0.03, 6.38+/-0.06, 6.22+/-0.05, 5.86+/-0.05 and 5.26+/-0.04 respectively. For comparison, the pD2 values for 5-HT and 5-carboxamidotryptamine (5-CT) were 7.52+/-0.02 and 7.55+/-0.03 respectively. In contrast to all other triptans tested, the concentration-response curve for eletriptan was biphasic (first phase: 0.01-3 microM, pD2 approximately 6.6; second phase: > or = 10 microM). Contractions to 5-HT, 5-CT, frovatriptan, zolmitriptan, rizatriptan, naratriptan, sumatriptan, almotriptan, and eletriptan (first phase) were antagonized by the 5-HT1B/1D receptor antagonist GR127935 (10 nM) and the 5-HT1B receptor antagonist SB216641 (10 nM). RT-PCR studies in guinea-pig iliac arteries showed a strong signal for the 5-HT1B receptor while expression of 5-HT1D and 5-HT1F receptors was not detected in any sample. The present results demonstrate that triptan-induced contraction in guinea-pig iliac arteries is mediated by the 5-HT1B receptor. The guinea-pig iliac artery may be used as a convenient in vitro model to study the (cardio)vascular side-effect potential of anti-migraine drugs of the triptan family.
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PMID:Involvement of 5-HT1B receptors in triptan-induced contractile responses in guinea-pig isolated iliac artery. 1518 63

The parasympathetic nervous system is probably involved in migraine pathogenesis. Its activation releases a mixture of signalling molecules including vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP), which subsequently stimulate VPAC(1), VPAC(2) and PAC(1) receptors. The objective of the present study was to investigate the in vivo effect of VIP, PACAP-27, PACAP-38, the selective VPAC(1) agonist ([Lys15, Arg16, Leu27]-VIP(1-7)-GRF(8-27)) and a PAC(1) agonist, maxadilan on rat middle meningeal artery (MMA) diameter using the closed cranial window model. Selective antagonists were used for further characterization of the responses. Reverse transcriptase-polymerase chain reaction experiments were also conducted to determine expression of mRNA of PACAP receptors in the MMA. The results showed that VIP, PACAP-38, PACAP-27 and the VPAC(1) specific agonist evoked significant dilations with the rank order of potency; VIP = PACAP-38 > PACAP-27 = [Lys15, Arg16, Leu27]-VIP(1-7)-GRF(8-27). Significant inhibition of dilation was only observed for the VPAC(1) antagonist PG97-269 on PACAP-38-induced dilation of MMA. The VPAC(2) antagonist PG99-465 and PAC(1) antagonist PACAP(6-38) did not significantly block VIP- or PACAP-induced dilation. Expression of mRNA of all three receptors was detected in the MMA. In conclusion, the VPAC(1) receptor seems to be predominant in mediating MMA dilation. A selective VPAC(1) antagonist may be a candidate molecule in the treatment of migraine headache.
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PMID:The in vivo effect of VIP, PACAP-38 and PACAP-27 and mRNA expression of their receptors in rat middle meningeal artery. 1922 Mar 6