bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of the cloned human NK3 receptor in Chinese Hamster Ovary cells characterized by the cellular acidification response using the Cytosensor microphysiometer
Authors: Jordan R E , Smart D , Grimson P , Suman‐Chauhan N , McKnight A T 
Published: January 2005

The aim of the present study was to validate the Cytosensor microphysiometer, a novel system that measures the extracellular acidification rate as a reliable index of the integrated functional response to receptor activation, as a method for studying NK3 receptor pharmacology, and then to use this system to assess the functional activity of novel compounds at this receptor.
The selective NK3 agonist senktide caused reproducible, concentration‐related increases in acidification ratein CHO‐NK3 cells, with a pEC50 value of 8.72±0.11 (n=15). [β‐Ala8]NKA(4–10), the selective NK2 agonist, elicited a much weaker response (pEC50=6.68±0.08, n=4), while the NK1‐selective agonist substance P methylester only caused a very weak response at concentrations 3 μM (n=2). The rank order of potency for the endogenous tachykinins NKB>NKA>substance P (n=3) confirmed the response was mediated by the NK3 receptor. Moreover, the actual potencies obtained were consistent with affinities measured in radioligand binding studies.
The novel compounds PD156319‐121 (0.3–1 μM), PD161182 (10–300 nM), PD168001 (10–100 nM) and PD168073 (10–100 nM) all acted as surmountable antagonists of the senktide‐induced acidification response, with pA2 values of 7.49, 8.67, 9.17 and 9.25 respectively (n=3–5). In comparison the known NK3 antagonist SR142801 (10–100 nM) had a pA2 value of 8.83 (n=8) for the interaction with senktide. Again, these values are consistent with the radioligand binding data.
Amiloride (1 mM) inhibited the senktide‐induced acidification response by 68.3±3.3 (n=4), indicating that the Na+/H+ antiporter plays an important role in this response, and this is consistent with the importance of this antiporter in other acidification responses.
Inhibition of protein kinase C with staurosporine (0.1 μM), or depletion of the intracellular Ca2+ stores with thapsigargin (1 μM), both resulted in a reduction in the maximum response to senktide (63.3±1.7 and 68.9±3.2% respectively, n=3–5), and co‐application of these inhibitors abolished the response (n=3). This strongly suggested that the NK3 receptor was coupling via phospholipase C (PLC), as would be expected, although this could not be confirmed by the use of the putative PLC/PLA2 inhibitor U73122.
In conclusion, we have demonstrated the utility of the Cytosensor in the characterization of functional responses to agonists, and assessment of the affinities of antagonists in CHO cells expressing the human NK3, and have shown that our series of novel compounds are non‐peptide NK3 antagonists of high affinity, as exemplified by PD168073.

British Journal of Pharmacology (1998) 125, 761–766; doi:10.1038/sj.bjp.0702156
The development of overt diabetes in young Zucker Diabetic Fatty (ZDF) rats and the effects of chronic MCC‐555 treatment
Authors: Pickavance L , Widdowson P S , King P , Ishii S , Tanaka H , Williams G 
Published: January 2005

Young (6‐week‐old) pre‐diabetic Zucker Diabetic Fatty (ZDF) rats displaying impaired glucose tolerance (IGT), moderate hyperglycaemia and hyperinsulinaemia were treated with the novel thiazolidinedione, MCC‐555, for 28 days, during which time β‐cell failure and progression to overt diabetes occurs.
Treated ZDF rats exhibited consistently lower blood glucose levels than vehicle‐treated diabetic controls, with a delayed rise and lower plateau levels. MCC‐555 maintained plasma insulin levels throughout the treatment period, whereas these fell by 40% in untreated ZDF rats.
The rise in body weight was maintained in MCC‐555‐treated rats, whereas vehicle‐treated rats exhibited blunted body weight gain after 8 weeks of age. Daily food intake was higher in diabetic, as compared to non‐diabetic rats, but treatment did not modify food intake in diabetic rats. Water intake was lower in treated ZDF rats, concomitant with lowering of blood glucose.
The hyperinsulinaemic‐euglycaemic clamp technique was applied to all rats after treatment to examine the effects of MCC‐555 on insulin sensitivity. The glucose infusion rate to maintain normoglycaemia was lower in diabetic than in non‐diabetic rats, demonstrating reduced glucose entry into insulin‐sensitive tissues in diabetic rats. Increased glucose infusion rates were required to maintain euglycaemia in treated diabetic rats, demonstrating increased insulin sensitivity in these animals.
In conclusion, chronic MCC‐555 treatment of young ZDF rats displaying IGT attenuates the development of overt diabetes through improved insulin sensitivity and maintenance of β‐cell function. MCC‐555 may thus be beneficial in humans with IGT, to prevent or delay the progression of diabetes.

British Journal of Pharmacology (1998) 125, 767–770; doi:10.1038/sj.bjp.0702158
The mechanism of the nitric oxide‐mediated enhancement of tert‐butylhydroperoxide‐induced DNA single strand breakage
Authors: Guidarelli Andrea , Clementi Emilio , Sciorati Clara , Cantoni Orazio 
Published: January 2005

Caffeine (Cf) enhances the DNA cleavage induced by tert‐butylhydroperoxide (tB‐OOH) in U937 cells via a mechanism involving Ca2+‐dependent mitochondrial formation of DNA‐damaging species (Guidarelli et al., 1997b). Nitric oxide (NO) is not involved in this process since U937 cells do not express the constitutive nitric oxide synthase (cNOS).
Treatment with the NO donors S‐nitroso‐N‐acetyl‐penicillamine (SNAP, 10 μM), or S‐nitrosoglutathione (GSNO, 300 μM), however, potentiated the DNA strand scission induced by 200 μM tB‐OOH. The DNA lesions generated by tB‐OOH alone, or combined with SNAP, were repaired with superimposable kinetics and were insensitive to anti‐oxidants and peroxynitrite scavengers but suppressed by iron chelators.
SNAP or GSNO did not cause mitochondrial Ca2+ accumulation but their enhancing effects on the tB‐OOH‐induced DNA strand scission were prevented by ruthenium red, an inhibitor of the calcium uniporter of mitochondria. Furthermore, the enhancing effects of both SNAP and GSNO were identical to and not additive with those promoted by the Ca2+‐mobilizing agents Cf or ATP.
The SNAP‐ or GSNO‐mediated enhancement of the tB‐OOH‐induced DNA cleavage was abolished by the respiratory chain inhibitors rotenone and myxothiazol and was not apparent in respiration‐deficient cells.
It is concluded that, in cells which do not express the enzyme cNOS, exogenous NO enhances the accumulation of DNA single strand breaks induced by tB‐OOH via a mechanism involving inhibition of complex III.

British Journal of Pharmacology (1998) 125, 1074–1080; doi:10.1038/sj.bjp.0702159
The influence of lobeline on nucleus accumbens dopamine and locomotor responses to nicotine in nicotine‐pretreated rats
Authors: Benwell Maureen E M , Balfour David J K 
Published: January 2005

In vivo brain microdialysis was used to investigate the influence of lobeline on dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) overflow in the core of the nucleus accumbens of freely‐moving rats pretreated with nicotine (0.4 mg kg−1, s.c., once per day for 5 days). Locomotion was also recorded.
Lobeline, at doses of 0.7, 4.0 and 10.0 mg kg−1, i.p., failed to elicit any significant changes in extracellular dopamine or dihydroxyphenylacetic acid levels during the 60 min following its administration and did not stimulate locomotor.
The dopamine responses to nicotine (0.4 mg kg−1, s.c.), were abolished (P < 0.01) if the nicotine challenge was administered 10 min but not 60 min, after lobeline doses of 4.0 and 10.0 mg kg−1, i.p., but were unaffected following lobeline at the lowest dose tested (0.7 mg kg−1, i.p.) at either time. The increase in locomotor activity was significantly attenuated (P < 0.01), to a similar extent, when the nicotine was injected 10 min, but not 60 min, after all three doses of lobeline (0.7, 4.0 and 10.0 mg kg−1, i.p.) when compared with the saline‐treated rats.
The results suggest that lobeline is a short‐acting antagonist of the nicotinic AChRs which mediate the effects of nicotine on mesolimbic dopamine activity and locomotor stimulation.

British Journal of Pharmacology (1998) 125, 1115–1119; doi:10.1038/sj.bjp.0702161
Lack of effect of a selective vasopressin V1A receptor antagonist, SR 49,059, on potentiation by vasopressin of adrenoceptor‐mediated pressor responses in the rat mesenteric arterial bed
Authors: Heinemann Akos , Horina Gabi , Stauber Rudolf E , Pertl Christof , Holzer Peter , Peskar Bernhard A 
Published: January 2005

The vasopressin receptor subtype involved in the enhancement by vasopressin of adrenoceptor‐mediated vasoconstriction was investigated in rat isolated perfused mesenteric arteries.
[Arg8]vasopressin (1–10 nm) dose‐dependently increased the perfusion pressure and enhanced the pressor response to the adrenoceptor agonist methoxamine (40 nmol) or electrical stimulation of periarterial nerves (16 Hz), at the concentration of 10 nm of [Arg8]vasopressin up to 4 and 3 fold, respectively.
During prolonged exposure (45 min) the direct vasoconstrictor effect of [Arg8]vasopressin (10 nm) rapidly declined whereas the potentiation of methoxamine‐induced vasoconstriction was maintained.
The selective vasopressin V1A receptor antagonist SR 49,059 (1–3 nm) and the non‐selective V1A/B and oxytocin receptor antagonist [deamino‐Pen1,Tyr(Me)2,Arg8]vasopressin (15–45 nm) inhibited the direct vasoconstrictor action of [Arg8]vasopressin but had no effect on the enhancement of the pressor response to methoxamine or electrical stimulation.
The V1B receptor agonist [deamino‐Cys1,β‐(3‐pyridyl)‐D‐Ala2,Arg8]vasopressin (100–1000 nm) and the V2 receptor agonist [deamino‐Cys1,D‐Arg8]vasopressin (1–10 nm) were devoid of any pressor activity and did not potentiate methoxamine‐evoked vasoconstriction. In contrast, [1‐triglycyl,Lys8]vasopressin (100–1000 nm) potentiated the methoxamine responses without per se inducing vasoconstriction.
In arteries precontracted with methoxamine (7.5 μm) pressor responses to [Arg8]vasopressin (3–10 nm) were not inhibited by a dose of SR 49,059 (3 nm) which abolished the peptide's vasoconstrictor effect under control conditions.
These data show that the direct vasoconstrictor effect of [Arg8]vasopressin is mediated by V1A receptors while the enhancement of adrenoceptor‐mediated pressor responses is insensitive to V1A, V1B, and oxytocin receptor antagonists and is not mimicked by selective agonists of V1B and V2 receptors. In conclusion, an unusual interaction of vasopressin with V1A receptors, or even the existence of a novel receptor subtype, has to be considered.

British Journal of Pharmacology (1998) 125, 1120–1127; doi:10.1038/sj.bjp.0702167
Potentiation of adenosine A1 receptor‐mediated inositol phospholipid hydrolysis by tyrosine kinase inhibitors in CHO cells
Authors: Dickenson John M. , Hill Stephen J. 
Published: January 2005

The effect of protein tyrosine kinase inhibitors on human adenosine A1 receptor‐mediated [3H]‐inositol phosphate ([3H]‐IP) accumulation has been studied in transfected Chinese hamster ovary cells (CHO‐A1) cells.
In agreement with our previous studies the selective adenosine A1 receptor agonist N6‐cyclopentyladenosine (CPA) stimulated the accumulation of [3H]‐IPs in CHO‐A1 cells. Pre‐treatment with the broad spectrum tyrosine kinase inhibitor genistein (100 μM; 30 min) potentiated the responses elicited by 1 μM (199±17% of control CPA response) and 10 μM CPA (234±15%). Similarly, tyrphostin A47 (100 μM) potentiated the accumulation of [3H]‐IPs elicited by 1 μM CPA (280±32%).
Genistein (EC50=13.7±1.2 μM) and tyrphostin A47 (EC50=10.4±3.9 μM) potentiated the [3H]‐IP response to 1 μM CPA in a concentration‐dependent manner.
Pre‐incubation with the inactive analogues of genistein and tyrphostin A47, daidzein (100 μM; 30 min) and tyrphostin A1 (100 μM; 30 min), respectively, had no significant effect on the accumulation of [3H]‐IPs elicited by 1 μM CPA.
Genistein (100 μM) had no significant effect on the accumulation of [3H]‐IPs produced by the endogenous thrombin receptor (1 u ml−1; 100±10% of control response). In contrast, tyrphostin A47 produced a small augmentation of the thrombin [3H]‐IP response (148±13%).
Genistein (100 μM) had no effect on the [3H]‐IP response produced by activation of the endogenous Gq‐protein coupled CCKA receptor with the sulphated C‐terminal octapeptide of cholecystokinin (1 μM CCK‐8; 96±6% of control). In contrast, tyrphostin A47 (100 μM) caused a small but significant increase in the response to 1 μM CCK‐8 (113±3% of control).
The phosphatidylinositol 3‐kinase inhibitor LY 294002 (30 μM) and the MAP kinase kinase inhibitor PD 98059 (50 μM) had no significant effect on the [3H]‐IP responses produced by 1 μM CPA and 1 μM CCK‐8.
These observations suggest that a tyrosine kinase‐dependent pathway may be involved in the regulation of human adenosine A1 receptor mediated [3H]‐IP responses in CHO‐A1 cells.

British Journal of Pharmacology (1998) 125, 1049–1057; doi:10.1038/sj.bjp.0702170
Potentiating action of MKC‐242, a selective 5‐HT1A receptor agonist, on the photic entrainment of the circadian activity rhythm in hamsters
Authors: Moriya T , Yoshinobu Y , Ikeda M , Yokota S , Akiyama M , Shibata S 
Published: January 2005

Serotonergic projections from the midbrain raphe nuclei to the suprachiasmatic nuclei (SCN) are known to regulate the photic entrainment of circadian clocks. However, it is not known which 5‐hydroxytryptamine (5‐HT) receptor subtypes are involved in the circadian regulation. In order to verify the role of 5‐HT1A receptors, we examined the effects of 5‐{3‐[((2S)‐1,4‐benzodioxan‐2‐ylmethyl)amino]propoxy}‐1,3‐benzodioxole HCl (MKC‐242), a selective 5‐HT1A receptor agonist, on photic entrainment of wheel‐running circadian rhythms of hamsters.
MKC‐242 (3 mg kg−1, i.p.) significantly accelerated the re‐entrainment of wheel‐running rhythms to a new 8 h delayed or advanced light‐dark cycle.
MKC‐242 (3 mg kg−1, i.p.) also potentiated the phase advance of the wheel‐running rhythm produced by low (5 lux) or high (60 lux) intensity light pulses. In contrast, 8‐hydroxy‐dipropylaminotetralin (8‐OH‐DPAT)(5 mg kg−1, i.p.), a well known 5‐HT1A/5‐HT7 receptor agonist, only suppressed low intensity (5 lux) light‐induced phase advances.
The potentiating actions of MKC‐242 on light pulse‐induced phase advances were observed even when injected 20 or 60 min after the light exposure.
The potentiating action of MKC‐242 was antagonized by WAY100635, a selective 5‐HT1A receptor blocker, but not by ritanserin, a 5‐HT2/5‐HT7 receptor blocker, indicating that MKC‐242 is activating 5‐HT1A receptors.
Light pulse‐induced c‐fos expression in the SCN and the intergeniculate leaflet (IGL) were unaffected by MKC‐242 (3 mg kg−1, i.p.).
HPLC analysis demonstrated that MKC‐242 (3 mg kg−1, i.p.) decreased the 5‐HIAA content in the SCN.
The present results suggest that presynaptic 5‐HT1A receptor activation may be involved in the potentiation of photic entrainment by MKC‐242 in hamsters.

British Journal of Pharmacology (1998) 125, 1281–1287; doi:10.1038/sj.bjp.0702176
Exogenous and endogenous catecholamines inhibit the production of macrophage inflammatory protein (MIP) 1α via a β adrenoceptor mediated mechanism
Authors: Haskó György , Shanley Thomas P , Egnaczyk Greg , Németh Zoltán H , Salzman Andrew L , Vizi E Sylvester , Szabó Csaba 
Published: January 2005

Noradrenaline (NA) and adrenaline (Ad) are modulators of cytokine production. Here we investigated the role of these neurotransmitters in the regulation of macrophage inflammatory protein (MIP)‐1α expression.
Pretreatment of RAW 264.7 macrophages with NA or Ad decreased, in a concentration‐dependent manner (1 nm–100 μm), MIP‐1α release induced by bacterial lipopolysaccharide (LPS 10 ng ml−1 LPS). The effect of NA was reversed by the selective β‐adrenoceptor antagonist propranolol (10 μm), but not by the α‐adrenoceptor antagonist phentolamine (10 μm).
In the concentration range of 10 nm–10 μm, isoproterenol, a β‐adrenoceptor agonist, but not phenylephrine (a selective α1‐adrenoceptor agonist) or UK‐14304 (a selective α2‐adrenoceptor agonist) mimicked the inhibitory effects of catecholamines on MIP‐1α production. Increases in intracellular cyclic adenosine monophosphate, elicited either by the selective type IV phosphodiesterase inhibitor rolipram (0.1–10 μm), or by prostaglandin E2, (10 nm–10 μm) decreased MIP‐1α release, suggesting that increased cyclic AMP may contribute to the suppression of MIP‐1α release by β‐adrenoceptor stimulation.
Northern blot analysis demonstrated that NA (100 nm–10 μm), Ad, isoproterenol, as well as rolipram (100 nm–10 μm) decreased LPS‐induced MIP‐1α mRNA accumulation. NA and Ad (1–100 μm) also decreased MIP‐1α production in thioglycollate‐elicited murine peritoneal macrophages.
Pretreatment of mice with either isoproterenol (10 mg kg−1, i.p.) or rolipram (25 mg kg−1, i.p.) decreased LPS‐induced plasma levels of MIP‐1α, while propranolol (10 mg kg−1, i.p.) augmented the production of this chemokine, confirming the role of a β‐adrenoceptor mediated endogenous catecholamine action in the regulation of MIP‐1α production in vivo.
Thus, based on our data we conclude that catecholamines are important endogenous regulators of MIP‐1α expression in inflammation.

British Journal of Pharmacology (1998) 125, 1297–1303; doi:10.1038/sj.bjp.0702179
Adenosine A1 receptor‐mediated excitation of nociceptive afferents innervating the normal and arthritic rat knee joint
Authors: Dowd E , McQueen D S , Chessell I P , Humphrey P P A 
Published: January 2005

We tested the hypothesis that adenosine excites nociceptive primary afferents innervating the knee joint.
Neuronal recordings were made from fine nerve filaments innervating the knee joint in rats anaesthetized with pentobarbitone. Drugs were injected close‐arterially (i.a.) or into the articular space (i.art.). We studied normal and chronically inflamed arthritic joints, the latter 14–21 days after a single intra‐articular injection of Freund's Complete Adjuvant, performed under halothane anaesthesia.
Adenosine injected i.a. caused delayed (approximately 10 s) excitation of the majority of polymodal C‐fibre afferents, and had similar effects when injected directly into the joint.
Adenosine triphosphate (ATP) had biphasic effects on discharge, a fast (<1 s) excitation was followed by a delayed increase similar to that seen with adenosine.
The adenosine A1 receptor agonists N6‐cyclopentyladenosine (CPA) and N‐[(1S,trans)‐2‐hydroxypentyl] adenosine (GR79236) also excited the C‐fibre afferents. The A1 antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX) antagonized the responses evoked by adenosine, CPA, and the delayed increase seen after ATP, indicating that excitation of the nociceptive afferents was mediated via adenosine A1 receptors.
Adenosine and ATP evoked delayed excitatory effects of similar magnitude, regardless of whether or not the knee joint was chronically inflamed. The increased basal discharge observed in arthritic joints was unaffected by DPCPX, which implies that the increase in spontaneous activity associated with arthritis is unlikely to involve tonically released adenosine.
The results support the hypothesis that adenosine excites primary afferent nociceptive nerve terminals in the rat knee joint, an effect mediated by adenosine A1 receptors. ATP, adenosine, and A1 receptors may play a role in generating the peripheral nociceptive (pain) signal.

British Journal of Pharmacology (1998) 125, 1267–1271; doi:10.1038/sj.bjp.0702185
Evidence that [Phe1ψ(CH2‐NH)Gly2]nociceptin‐(1‐13)‐NH2, a peripheral ORL‐1 receptor antagonist, acts as an agonist in the rat spinal cord
Authors: Carpenter Kate J. , Dickenson Anthony H. 
Published: January 2005

[Phe1 ψ(CH2‐NH)Gly2]nociceptin‐(1‐13)‐NH2, a pseudopeptide analogue of nociceptin is an antagonist in peripheral assays. Here, using in vivo electrophysiological recordings of dorsal horn neurones, [Phe1 ψ(CH2‐NH)Gly2]nociceptin‐(1‐13)‐NH2 appears to have agonist activity after spinal administration. The noxious evoked activity of the neurones was inhibited by [Phe1 ψ(CH2‐NH)Gly2]nociceptin‐(1‐13)‐NH2, which was as potent as nociceptin itself.British Journal of Pharmacology (1998) 125, 949–952; doi:10.1038/sj.bjp.0702188
The activation of nitric oxide synthase by copper ion is mediated by intracellular Ca2+ mobilization in human pulmonary arterial endothelial cells
Authors: Demura Yoshiki , Ishizaki Takeshi , Ameshima Shingo , Okamura Seitarou , Hayashi Takio , Matsukawa Shigeru , Miyamori Isamu 
Published: January 2005

The aim of the study was to elucidate the vasodilatory mechanism due to Cu2+ by assessing nitric oxide (NO) production as determined by NOx (NO, NO2−, and NO3−) that is released from human pulmonary arterial endothelial cell (HPAEC) monolayers using a NO chemiluminescence analyzer, and also to assess Ca2+ movement using 45Ca and fura 2 in HPAEC.
Cu2+ (10−6–10−4 m) significantly increased NO production in a dose‐dependent manner when extracellular Ca2+ was present.
45Ca influx into the adherent cells was dose‐dependently enhanced by Cu2+ (10−6–10−4 m), but not by Mn2+, Zn2+ or Fe2+.
[Ca2+]i, measured by monitoring the fluorescence changes of fura 2, was significantly elevated in the presence of Cu2+.
The increase in [Ca2+]i induced by Cu2+ was inhibited by either diethyldithiocarbamate (DDC) or the depletion of extracellular Ca2+.
The dihydropyridine receptor agonist, BayK8644, significantly attenuated the Cu2+‐induced increase in [Ca2+]i in a dose dependent manner and nitrendipine or nifedipine, the dihydropyridine receptor antagonists, dose‐dependently inhibited a Cu2+‐induced increase in [Ca2+]i.
These results suggest that Cu2+ activates eNOS through the mechanism of [Ca2+]i elevation due to Ca2+ influx into HPAEC and that the Cu2+‐induced [Ca2+]i elevation in HPAEC is likely due to activation of the dihydropyridine‐like receptors.

British Journal of Pharmacology (1998) 125, 1180–1187; doi:10.1038/sj.bjp.0702197
A microdialysis study of the in vivo release of 5‐HT in the median raphe nucleus of the rat
Authors: Adell Albert , Artigas Francesc 
Published: January 2005

The present study has examined several characteristics of the release of 5‐HT in the median raphe nucleus in terms of its dependence of nerve impulse, provenance of a vesicular storage fraction as well as the regulatory role played by 5‐HT1A receptors.
Tetrodotoxin (1 μm) and reserpine (5 mg kg−1, i.p.) virtually suppressed the output of 5‐HT.
The administration of EEDQ (10 mg kg−1, i.p.) did not alter the basal release of 5‐HT but abolished the reduction of 5‐HT release induced by 8‐OH‐DPAT (0.1 mg kg−1, s.c.).
The perfusion of 1–100 μm of 8‐OH‐DPAT or the novel 5‐HT1A agonist BAY×3702 decreased the efflux of 5‐HT, whereas the perfusion of the 5‐HT1A antagonist WAY‐100635 failed to alter 5‐HT release.
The decrease in dialysate 5‐HT induced by 100 μm 8‐OH‐DPAT was reversed by the concurrent perfusion of 100 μm WAY‐100635. Also, the perfusion of 100 μm WAY‐100635 for 2 h inhibited partly the reduction of 5‐HT release evoked by the systemic administration of 8‐OH‐DPAT (0.1 mg kg−1).
These results indicate that extracellular 5‐HT in the median raphe nucleus is stored in vesicles and released in an impulse‐dependent manner. Also, the basal release of 5‐HT in the median raphe nucleus does not appear to be under the tonic control of somatodendritic 5‐HT1A receptors by endogenous 5‐HT. Instead, this feedback mechanism seems to be triggered when an excess of the transmitter or a 5‐HT1A agonist is present in the extracellular space of the median raphe nucleus.

British Journal of Pharmacology (1998) 125, 1361–1367; doi:10.1038/sj.bjp.0702206