Disease relevance of HTR1D

• Since 5-HT1D receptor mRNA and protein are expressed in trigeminal ganglia but not vascular smooth muscle, the 5-HT1D receptor subtype may become a useful therapeutic target for migraine and related headaches [1].
• These data indicate that the 5-HT1D receptor subtype plays a significant role in suppressing meningeal neurogenic inflammation and attenuating trigeminal nociception in these guinea pig models [1].

Psychiatry related information on HTR1D

• In guinea pigs, RU 24969 failed to affect PPI, although it did increase locomotor activity, indicating that RU 24969 may have activity at the 5-HT1D receptor [2].

High impact information on HTR1D

• Sequence and functional analysis of cloned guinea pig and rat serotonin 5-HT1D receptors: common pharmacological features within the 5-HT1D receptor subfamily [3].
• Effects of PNU-109,291, a selective 5-HT1D receptor agonist, on electrically induced dural plasma extravasation and capsaicin-evoked c-fos immunoreactivity within trigeminal nucleus caudalis [1].
• The 5-HT1D receptor antagonist GR-127,935 prevents inhibitory effects of sumatriptan but not CP-122,288 and 5-CT on neurogenic plasma extravasation within guinea pig dura mater [4].
• The selective 5-HT1B/D receptor antagonist, GR127935 (100-1000 nM), and the 5-HT1D receptor antagonist, ketanserin (300-1000 nM), had no significant effect on this release in either of these regions [5].
• Comparison of the deduced amino acid sequences of guinea pig 5-HT1B and 5-HT1D receptor subtypes show that they display overall and transmembrane (TM) identities of 63% and 77%, respectively [6].

Biological context of HTR1D

• Instead, 5-HT1D receptor binding sites should be redefined as [3H]5-HT-labeled binding sites displaced by 10(-5) M sumatriptan [7].
• Here we describe the cloning and sequencing by the polymerase chain reaction (PCR) method of two 5-HT1D receptor sequences of the third cytoplasmic loop in mouse, strongly suggesting the existence of two 5-HT1D receptor genes, located on chromosome 4 [8].

Anatomical context of HTR1D

• 5-Hydroxytryptamine (5-HT)-induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT1D receptor subtype [9].
• 3. L-694,247, like sumatriptan, displayed a similar efficacy to 5-HT in inhibiting forskolin-stimulated adenylyl cyclase in guinea-pig substantia nigra although L-694,247 (pEC50 = 9.1) was more potent than sumatriptan (6.2) in this 5-HT1D receptor mediated functional response [10].
• Both clones contain a conserved threonine residue in TM7, a structural feature imparting "5-HT1D receptor pharmacology". Guinea pig 5-HT1B and 5-HT1D receptor genes were transiently expressed in Cos-7 cells and their binding properties were evaluated using [3H]5-HT [6].
• The above results suggest that GMC2021 constricts carotid arteriovenous anastomoses partly by a 5-HT1D receptor and partly by another, probably novel, receptor and that GMC2021 should be able to abort migraine headaches in patients, with perhaps a less propensity for coronary side effects [11].
• The present study demonstrates that 5-HT1B- and 5-HT1D receptor mRNA is co-localized in serotonergic cell bodies of the guinea pig dorsal raphé nucleus [12].

Associations of HTR1D with chemical compounds

• The functional activity of this series of compounds is studied and demonstrates high 5-HT1D receptor potency and efficacy comparable to that of 5-HT [13].
• 1. It has previously been shown that the antimigraine drug, sumatriptan, a putative 5-HT1D receptor agonist, decreases porcine common carotid and arteriovenous anastomotic blood flows, but slightly increases the arteriolar (capillary) blood flow to the skin and ears [14].
• L-694,247: a potent 5-HT1D receptor agonist [10].
• Blockade of porcine carotid vascular response to sumatriptan by GR 127935, a selective 5-HT1D receptor antagonist [14].
• SB-216641A (N-[3-(2-dimethylamino) ethoxy-4-methoxy-phenyl] 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-car boxamide hydrochloride) (0.6-20.0 mg/kg i.p.), which is somewhat less selective (30 fold) for the 5-HT1B receptor over the 5-HT1D receptor had a similar effect (ED50 4.43 mg/kg) [15].

Regulatory relationships of HTR1D

• In the course of these studies, it was found that the purportedly selective 5-HT1D receptor antagonist GR127935 inhibited 5-HT1F receptor-stimulated [35S]GTPgammaS binding with a Ki of 39.6 +/- 9.5 nM [16].

Analytical, diagnostic and therapeutic context of HTR1D

• Co-localization of 5-HT1B- and 5-HT1D receptor mRNA in serotonergic cell bodies in guinea pig dorsal raphé nucleus: a double labeling in situ hybridization histochemistry study [12].
• Constriction of porcine arteriovenous anastomoses by indorenate is unrelated to 5-HT1A, 5-HT1B, 5-HT1C or 5-HT1D receptor subtypes [17].

References