bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional cross‐talk between endothelial muscarinic and α2‐adrenergic receptors in rabbit cerebral arteries
Authors: Thorin Eric 
Published: January 2005

Interactions between two classes of receptors have been observed in several cell lines and preparations. The aim of this work was to assess the impact of simultaneous stimulation of endothelial muscarinic and α2‐adrenergic receptors (α2‐AR) on vascular reactivity.
Rabbit middle cerebral arteries were isolated and changes in isometric tension were recorded in the presence of indomethacin.
Inhibition of nitric oxide (NO) synthase with Nω‐nitro‐l‐arginine (l‐NOARG, 100 μmol l−1) revealed α‐AR‐dependent contractions. Pre‐addition of acetylcholine (ACH, 1 μmol l−1) augmented oxymetazoline (OXY, 10 μmol l−1, α2‐AR agonist)‐, but decreased phenylephrine (PE, 10 μmol l−1, α1‐AR agonist)‐induced contraction (P < 0.05). The effects of ACH were endothelium‐dependent.
Vessels were precontracted with 40 mmol l−1 KCl‐physiological salt solution (PSS) in the absence of l‐NOARG, or PE or OXY in the presence of l‐NOARG. In the presence of high external K+ or PE, ACH induced a potent relaxation (P < 0.05). In the presence of OXY, however, ACH mediated contraction (P < 0.05).
After pertussis toxin (PTX, inactivator of Gαi/o proteins) pre‐treatment, α2‐AR‐dependent contractions were abolished. Forty mmol l−1 KCl‐PSS induced contraction was not altered by PTX whereas ACH‐induced relaxation was augmented (P < 0.05).
To investigate if endothelin‐1 (ET‐1) intervened in the endothelium‐dependent contractile response to ACH in the presence of OXY‐dependent tone, vessels were incubated in the presence of BQ123 (1 μmol l−1), an ETA receptor antagonist. OXY‐mediated tone was not affected by BQ123; however, ACH‐induced contraction was reversed to a relaxation (P < 0.05).
These data indicate that activation of endothelial α2‐AR triggers an endothelium‐dependent, ET‐1 mediated, contraction to ACH. This suggests that activation of α2‐AR affects muscarinic receptor/G protein coupling leading to an opposite biological effect.

British Journal of Pharmacology (1998) 125, 1188–1193; doi:10.1038/sj.bjp.0702199
Developmental changes in endothelium‐dependent vasodilation and the influence of superoxide anions in perinatal rabbit pulmonary arteries
Authors: Morecroft Ian , MacLean Margaret R 
Published: January 2005

ACh‐induced vasodilation was investigated in pulmonary arteries from 8 and 2 day pre‐term foetal, neonatal (0–12 h and 4 day old) and adult rabbits. The effects of superoxide anion generation [with hypoxanthine (HX, 0.1 mm)/xanthine oxidase (XO, 15 mu ml−1)], endogenous superoxide dismutase (SOD) inhibition [with the Cu‐Zn SOD inhibitor triethylenetetramine (TETA, 1 mm)], endogenous superoxide anion scavenging [by superoxide dismutase (SOD, 50 u ml−1)] and inhibition of endothelial nitric oxide synthase (eNOS) [with, Nω‐nitro‐l‐arginine methylester (l‐NAME, 0.1 mm)], on basal and ACh‐induced NO activity were studied by examining phenylephrine‐induced contraction and ACh‐induced vasodilation respectively.
l‐NAME and endothelium removal abolished all ACh‐induced vasodilation and 1 μm sodium nitroprusside fully dilated all vessels. ACh‐induced vasodilation was absent in the 8 day pre‐term foetus and 0–12 h neonate but present at all other ages. l‐NAME itself contracted 2 day pre‐term foetal vessels. At 0–12 h, SOD, but not the phosphodiesterase 5 inhibitor zaprinast (1 μm), uncovered ACh‐induced vasodilation. At this age SOD reduced phenylephrine‐induced contraction which was not influenced by TETA, l‐NAME or HX/XO, and l‐NAME itself did not cause contraction. This suggests both ACh‐induced and basal NO activity are compromise in these vessels by endogenous superoxide anion production and deficiencies in endogenous SOD activity.
In 4 day vessels, but not adult vessels, l‐NAME, TETA and HX/XO augmented contractions to phenylephrine, and l‐NAME itself induced vasoconstriction, suggesting that basal NO and SOD activities were present by 4 days but were not evident in the adult. ACh‐induced NO activity, and the influence of endogenous SOD on this, were present in the adult (and 4 day) vessels as superoxide generation with HX/XO significantly reduced ACh‐induced vasodilation and this effect was inhibited by SOD and augmented by TETA.
Increased oxygen tensions >500 mmHg attenuated ACh‐induced vasodilation in the foetal but not neonatal rabbits. Raising the oxygen tension from ∼20 to ∼120 mmHg revealed ACh‐induced vasodilation in the 8 day pre‐term vessels.
In summary, superoxide anion accumulation combined with deficiencies in SOD activity may transiently compromise basal and ACh‐induced NO activity at birth. Experimental oxygen tensions markedly influence ACh‐induced vasodilation in foetal rabbit pulmonary arteries.

British Journal of Pharmacology (1998) 125, 1585–1593; doi:10.1038/sj.bjp.0702217
Modulation of inhibitory post‐synaptic currents (IPSCs) in mouse cerebellar Purkinje and basket cells by snake and scorpion toxin K+ channel blockers
Authors: Southan Andrew P , Robertson Brian 
Published: January 2005

Using an in vitro mouse cerebellar slice preparation and whole‐cell electrophysiological recording techniques we have characterized Purkinje and basket cell inhibitory post‐synaptic currents (IPSCs), and examined the effects of a number of selective peptidergic K+ channel blockers.
Spontaneous IPSC amplitude ranged from ∼10 pA up to ∼3 nA for both cell types [mean values: Purkinje cells −122.8±20.0 pA (n=24 cells); basket cells −154.8±15.9 pA (n=26 cells)]. Frequency varied from ∼3 up to ∼40 Hz, [mean values: basket cells 14.9±1.7 Hz (n=26 cells); Purkinje cells 17.9±2.2 Hz (n=24 cells)]. 5 μm bicuculline eliminated virtually all spontaneous currents.
IPSC rise times were fast (∼0.6 ms) and the decay phase was best fit with the sum of two exponential functions (τ1 and τ2: ∼4 ms and ∼20 ms, n = 40; for both cell types).
The snake toxins alpha‐dendrotoxin (α‐DTX) and toxin K greatly enhanced IPSC frequency and amplitude in both cell types; the closely related homologues toxin I and gamma‐dendrotoxin (γ‐DTX) produced only marginal enhancements (all at 200 nm).
Two scorpion toxins, margatoxin (MgTX) and agitoxin‐2 (AgTX‐2) had only minor effects on IPSC frequency or amplitude (both at 10 nm).
Low concentrations of tetraethylammonium (TEA; 200 μm) had no overall effect on cerebellar IPSCs, whilst higher concentrations (10 mm) increased both the frequency and amplitude.
The results suggest that native K+ channels, containing Kv1.1 and Kv1.2 channel subunits, play an influential role in controlling GABAergic inhibitory transmission from cerebellar basket cells.

British Journal of Pharmacology (1998) 125, 1375–1381; doi:10.1038/sj.bjp.0702218
Distinct PKC isoforms mediate the activation of cPLA2 and adenylyl cyclase by phorbol ester in RAW264.7 macrophages
Authors: Lin Wan‐W , Chen Bin C 
Published: January 2005

The modulatory effects of protein kinase C (PKC) on the activation of cytosolic phospholipase A2 (cPLA2) and adenylyl cyclase (AC) have recently been described. Since the signalling cascades associated with these events play critical roles in various functions of macrophages, we set out to investigate the crosstalk between PKC and the cPLA2 and AC pathways in mouse RAW 264.7 macrophages and to determine the involvement of individual PKC isoforms. The cPLA2 and AC pathways were studied by measuring the potentiation by the phorbol ester PMA of ionomycin‐induced arachidonic acid (AA) release and prostagladin E1 (PGE1)‐stimulated cyclic AMP production, respectively.
PMA at 1 μm caused a significant increase in AA release both in the presence (371%) and absence (67%) of ionomycin induction, while exposure of RAW 264.7 cells to PMA increased PGE1 stimulation of cyclic AMP levels by 208%.
Treatment of cells with staurosporine and Ro 31‐8220 inhibited the PMA‐induced potentiation of both AA release and cyclic AMP accumulation, while Go 6976 (an inhibitor of classical PKC isoforms) and LY 379196 (a specific inhibitor of PKCβ) inhibited the AA response but failed to affect the enhancement of the cyclic AMP response by PMA.
Long term pretreatment of cells with PMA abolished the subsequent effect of PMA in potentiating AA release, but only inhibited the cyclic AMP response by 42%.
Neither PD 98059, an inhibitor of MEK, nor genistein, an inhibitor of tyrosine kinases, had any effect on the ability of PMA to potentiate AA or cyclic AMP production.
The potentiation of AA release, but not of cyclic AMP formation, by PMA was sensitive to inhibition by wortmannin. This effect was unrelated to the inhibition of PKC activation as deduced from the translocation of PKC activity to the cell membrane.
Western blot analysis revealed the presence of eight PKC isoforms (α, βI, βII, δ, ε, μ λ and ξ) in RAW 264.7 cells and PMA was shown to induce the translocation of the α, βI, βII, δ, ε and μ isoforms from the cytosol to the cell membrane within 2 min.
Pretreatment of cells with PMA for 2–24 h resulted in a time‐dependent down‐regulation of PKCα, βI, βII, and δ expression, while the levels of the other four PKC isozymes were unchanged after PMA treatment for 24 h. A decrease in the potentiation of AA release by PMA was observed, concomitant with the time‐dependent down‐regulation of PKC.
These results indicate that PKCβ has a crucial role in the mediation of cPLA2 activation by the phorbol ester PMA, whereas PMA utilizes PKC ε and/or μ to up‐regulate AC activity.

British Journal of Pharmacology (1998) 125, 1601–1609; doi:10.1038/sj.bjp.0702219
Pharmacological characterization of the human vasopressin receptor subtypes stably expressed in Chinese hamster ovary cells
Authors: Tahara Atsuo , Saito Masayuki , Sugimoto Toru , Tomura Yuichi , Wada Koh‐ichi , Kusayama Toshiyuki , Tsukada Junko , Ishii Noe , Yatsu Takeyuki , Uchida Wataru , Tanaka Akihiro 
Published: January 2005

Three subtypes of human (h) arginine vasopressin (AVP) receptors, hV1A, hV1B and hV2, were stably expressed in Chinese hamster ovary (CHO) cells and characterized by [3H]‐AVP binding studies. In addition, the coupling of the expressed receptor protein to a variety of signal transduction pathways was investigated.
Scatchard analysis of saturation isotherms for the specific binding of [3H]‐AVP to membranes, prepared from CHO cells transfected with hV1A, hV1B and hV2 receptors, yielded an apparent equilibrium dissociation constant (Kd) of 0.39, 0.25 and 1.21 nm and a maximum receptor density (Bmax) of 1580 fmol mg−1 protein, 5230 fmol mg−1 protein and 7020 fmol mg−1 protein, respectively. Hill coefficients did not differ significantly from unity, suggesting binding to homogenous, non‐interacting receptor populations.
Pharmacological characterization of the transfected human AVP receptors was undertaken by measuring the relative ability of nonpeptide AVP receptor antagonists, YM087, OPC‐21268, OPC‐31260, SR 49059 and SR 121463A, to inhibit binding of [3H]‐AVP. At hV1A receptors, the relative order of potency was SR49059>YM087>OPC‐31260>SR 121463A>>OPC‐21268 and at hV2 receptors, YM087=SR 121463A>OPC‐31260>SR 49059>>OPC‐21268. In contrast, the relative order of potency, at hV1B receptors, was SR 49059>>SR 121463A=YM087=OPC‐31260=OPC‐21268.
In CHO cells expressing either hV1A or hV1B receptors, AVP caused a concentration‐dependent increase in intracellular Ca2+ concentration ([Ca2+]i) with an EC50 value of 1.13 nm and 0.90 nm, respectively. In contrast, stimulation of CHO cells expressing hV2 receptors resulted in an accumulation of cyclic AMP with an EC50 value of 2.22 nm. The potency order of antagonists in inhibiting AVP‐induced [Ca2+]i or cyclic AMP response was similar to that observed in radioligand binding assays.
In conclusion, we have characterized the pharmacology of human cloned V1A, V1B and V2 receptors and used these to determine the affinity, selectivity and potency of nonpeptide AVP receptor antagonists. Thus they may prove to be a valuable tool in further examination of the physiological and pathophysiological roles of AVP.

British Journal of Pharmacology (1998) 125, 1463–1470; doi:10.1038/sj.bjp.0702220
Desensitization of the histamine H1‐receptor and transcriptional down‐regulation of histamine H1‐receptor gene expression in bovine tracheal smooth muscle
Authors: Pype J. L. , Mak J. C. W. , Dupont L. J. , Verleden G. M. , Barnes P. J. 
Published: January 2005

We have investigated the role of protein kinase C (PKC) in the desensitization of histamine H1‐receptors and in the expression of the histamine H1‐receptor gene in airway smooth muscle.
Prolonged 4β‐phorbol 12,13 dibutyrate (PDBu) pretreatment (4 h, 100 nm–1 μm) of bovine trachealis caused a concentration‐dependent loss of contraction in response to histamine H1‐receptor stimulation, which was associated with a concentration‐dependent decrease in histamine‐induced total [3H]‐inositol phosphates accumulation. In contrast, the responses to sodium fluoride, a direct G‐protein activator, were unalterd by PDBu (100–300 nm) pre‐incubation and only slightly reduced following incubation with 1 μm PDBu.
A selective PKC inhibitor, GF 109203X, partially blocked the PDBu (1 μm)‐induced desensitization and completely blocked the effect of 100 nm PDBu, confirming the involvement of PKC.
Binding experiments using [3H]‐pyrilamine revealed a class of high‐affinity binding sites within the range for the histamine H1 receptor in airway smooth muscle. PDBu (1 μm) pretreatment for 4 h did not change the number of histamine H1 receptors.
PDBu (1 μm) exposure caused a time‐dependent reduction in the steady‐state levels of histamine H1‐receptor mRNA, which was inhibited by pre‐incubation with GF 109203X and by cycloheximide, a protein synthesis inhibitor.
Nuclear run‐on assays revealed a 50% reduction in the rate of histamine H1‐receptor gene transcription after 17 h PDBu pretreatment, whereas mRNA stability was not affected by PDBu pretreatment (17 h).
In conclusion, we have shown a PKC‐mediated desensitization of the histamine H1‐receptor in BTSM and a transcriptional down‐regulation of the histamine H1‐receptor gene expression, which requires new protein synthesis.

British Journal of Pharmacology (1998) 125, 1477–1484; doi:10.1038/sj.bjp.0702222
Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells in vivo
Authors: He Shaoheng , Walls Andrew F. 
Published: January 2005

The roles of chymase in acute allergic responses are not clear, despite the relative abundance of this serine proteinase in the secretory granules of human mast cells. We have isolated chymase to high purity from human skin tissue by heparin‐agarose affinity chromatography and Sephacryl S‐200 gel filtration procedures, and have investigated the ability of human mast cell chymase to stimulate cell accumulation following injection into laboratory animals.
Injection of chymase provoked marked neutrophilia and eosinophilia in the skin of Dunkin Hartley guinea‐pigs. Compared with saline injected control animals, there were some 60 fold more neutrophils and 12 fold more eosinophils present at the injection site.
Following injection of chymase into the peritoneum of BALB/c mice, there were up to 700 fold more neutrophils, 21 fold more eosinophils, 19 fold more lymphocytes and 7 fold more macrophages recovered than from saline injected controls at 16 h. Doses of chymase as low as 5 ng (1.7×10−13 mole) stimulated an inflammatory infiltrate, and significant neutrophilia was elicited within 3 h.
The chymase induced cell accumulation in both the guinea‐pig and mouse models was dependent on an intact catalytic site, being reduced by co‐injection of proteinase inhibitors or heat inactivation of the enzyme.
Co‐injection of histamine or heparin significantly reduced the chymase induced neutrophil accumulation, whereas neither histamine nor heparin by themselves had any effect on the accumulation of nucleated cells. No synergistic or antagonist interactions between chymase and tryptase were observed when these two major mast cell proteinases were co‐injected into the mouse peritoneum.
Our findings suggest that chymase may provide an potent stimulus for inflammatory cell recruitment following mast cell activation.

British Journal of Pharmacology (1998) 125, 1491–1500; doi:10.1038/sj.bjp.0702223
Involvement of 5‐HT6 receptors in nigro‐striatal function in rodents
Authors: Bourson Anne , Boess Frank G , Bös Michael , Sleight Andrew J 
Published: January 2005

4‐Amino‐N‐(2,4 bis‐methylamino‐pyrimidin‐4‐yl) benzene sulphonamide (Ro 04‐6790) is a potent, selective and competitive antagonist for the 5‐HT6 receptor which can be detected in the cerebro‐spinal fluid (CSF) of rats following intraperitoneal administration. Since 5‐HT6 receptor mRNA and 5‐HT6 receptor‐like immunoreactivity have been shown to be present in the striatum, the purpose of the present study was to evaluate the effect of 5‐HT6 receptor antagonism on haloperidol‐ and SCH 23390‐induced catalepsy in mice and on the turning behaviour of rats with unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the medial forebrain bundle.
Ro 04‐6790 (3, 10 and 30 mg kg−1 i.p.) did not induce catalepsy and had no effect on catalepsy induced by either haloperidol or SCH 23390.
Ro 04‐6790 (3, 10 and 30 mg kg−1 i.p.) did not itself induce rotational behaviour in rats with unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the medial forebrain bundle nor did it affect the rotational behaviour induced by either L‐Dopa or amphetamine.
5‐HT6 receptor antagonism inhibited the rotational behaviour of 6‐OHDA lesioned rats induced by treatment with the muscarinic antagonists scopolamine and atropine.
The data support earlier conclusions from experiments with antisense oligonucleotides that the 5‐HT6 receptor is involved in the control of acetylcholine neurotransmission in the rat brain.

British Journal of Pharmacology (1998) 125, 1562–1566; doi:10.1038/sj.bjp.0702230
Modelling of the pharmacodynamic interaction between phenytoin and sodium valproate
Authors: Paschoa O E Della , Voskuyl R A , Danhof M 
Published: January 2005

Treatment of epilepsy with a combination of antiepileptic drugs remains the therapeutic choice when monotherapy fails. In this study, we apply pharmacokinetic‐pharmacodynamic modelling to characterize the interaction between phenytoin (PHT) and sodium valproate (VPA).
Male Wistar rats received a 40 mg kg−1 intravenous dose of PHT over 5 min either alone or in combination with an infusion of VPA resulting in a steady‐state concentration of 115.5±4.9 μg ml−1. A control group received only the infusion of VPA. The increase in the threshold for generalized seizure activity (ΔTGS) was used as measure of the anticonvulsant effect.
PHT pharmacokinetics was described by a pharmacokinetic model with Michaelis‐Menten elimination. The concentration‐time course and plasma protein binding of PHT were not altered by VPA. The pharmacokinetic parameters Vmax and Km were, respectively, 294±63 μg min−1 and 7.8±2.4 μg ml−1 in the absence of VPA and 562±40 μg min−1 and 15.6±0.9 μg ml−1 upon administration in combination with VPA.
A delay of the onset of the effect relative to plasma concentrations of PHT was observed. The assessment of PHT concentrations at the effect site was based on the effect‐compartment model, yielding mean ke0 values of 0.128 and 0.107 min−1 in the presence and absence of VPA, respectively.
A nonlinear relationship between effect‐site concentration and the increase in the TGS was observed. The concentration that causes an increase of 50% in the baseline TGS (EC50%TGS) was used to compare drug potency. A shift of EC50%TGS from 13.27±3.55 to 4.32±0.52 μg ml−1 was observed upon combination with VPA (P<0.01).
It is concluded that there is a synergistic pharmacodynamic interaction between PHT and VPA in vivo.

British Journal of Pharmacology (1998) 125, 1610–1616; doi:10.1038/sj.bjp.0702235
Studies of the antagonist actions of (RS)‐2‐amino‐3‐[5‐tert‐butyl‐3‐(phosphonomethoxy)‐4‐isoxazolyl]propionic acid (ATPO) on non‐NMDA receptors in cultured rat neurones
Authors: Dai W‐M , Ebert B , Madsen U , Lambert J D C 
Published: January 2005

Whole‐cell patch‐clamp recordings from single cultured cortical neurones have been used to study the action of (RS)‐2‐amino‐3‐[5‐tert‐butyl‐3‐(phosphonomethoxy)‐4‐isoxazolyl]propionic acid (ATPO), which has previously been proposed to be a potent selective antagonist of 2‐amino‐3‐(3‐hydroxy‐5‐methyl‐4‐isoxazolyl)propionic acid (AMPA) receptors.
ATPO competitively reduced peak responses evoked by semi‐rapid applications of AMPA (Ki=16 μm) but had variable effects on plateau responses, which were on average unchanged. Following blockade of AMPA receptor desensitization by cyclothiazide (CTZ, 100 μm), the plateau responses were reduced by ATPO to a similar extent as the peak responses, indicating that ATPO reduces desensitization of AMPA receptors.
Semi‐rapid application of kainic acid (KA) and the KA receptor‐selective agonist, (2S,4R)‐4‐methylglutamic acid (MeGlu) evoked non‐desensitizing responses which were competitively antagonized by ATPO (Ki values: 27 and 23 μm, respectively).
Responses to MeGlu were unaffected by CTZ (100 μm), but potentiated 3 fold following blockade of KA receptor desensitization by concanavalin A (Con A, 300 μg ml−1). Responses of spinal cord neurones to MeGlu were blocked by ATPO to a similar extent before and after blockade of KA receptor desensitization by Con A.
Although selectively potentiated by Con A, plateau responses to MeGlu were reduced by 69.6% by the AMPA selective antagonist, GYKI 53655 (10 μm). The remaining component was further reduced by ATPO with a Ki of 36 μm, which was not significantly different from that in the absence of GYKI 53655, but was greater than that on responses to AMPA.
It is concluded that ATPO is a moderate‐potency competitive inhibitor of naturally expressed non‐NMDA receptors.

British Journal of Pharmacology (1998) 125, 1517–1528; doi:10.1038/sj.bjp.0702236
Facilitation and inhibition of male rat ejaculatory behaviour by the respective 5‐HT1Aand 5‐HT1Breceptor agonists 8‐OH‐DPAT and anpirtoline, as evidenced by use of the corresponding new and selective receptor antagonists NAD‐299 and NAS‐181
Authors: Hillegaart Viveka , Ahlenius Sven 
Published: January 2005

Ejaculatory problems and anorgasmia are well‐known side‐effects of the SSRI antidepressants, and a pharmacologically induced increase in serotonergic neurotransmission inhibits ejaculatory behaviour in the rat. In the present study the role of 5‐HT1Aand 5‐HT1Breceptors in the mediation of male rat ejaculatory behaviour was examined by use of selective agonists and antagonists acting at these 5‐HT receptor subtypes.The 5‐HT1Areceptor agonist 8‐OH‐DPAT (0.25–4.00 μmol kg−1s.c.) produced an expected facilitation of the male rat ejaculatory behaviour, and this effect was fully antagonized by pretreatment with the new selective 5‐HT1Areceptor antagonist (R)‐3‐N,N‐dicyclobutylamino‐8‐fluoro‐3,4‐dihydro‐2H‐1‐benzopyran‐5‐carboxamide hydrogen (2R,3R) tartrate monohydrate (NAD‐299) (1.0 μmol kg−1s.c.). NAD‐299 by itself (0.75–3.00 μmol kg−1s.c.) did not affect the male rat ejaculatory behaviour.The 5‐HT1Breceptor agonist anpirtoline (0.25–4.00 μmol kg−1s.c.) produced a dose‐dependent inhibition of the male rat ejaculatory behaviour, and this effect was fully antagonized by pretreatment with the 5‐HT1Breceptor antagonist isamoltane (16 μmol kg−1s.c.) as well as by the new and selective antagonist (R)‐(+)‐2‐(3‐morpholinomethyl‐2H‐chromene‐8‐yl)oxymethylmorpholino methansulphonate (NAS‐181) (16 μmol kg−1s.c.). Isamoltane (1.0–16.0 μmol kg−1s.c.) and NAD‐181 (1.0–16.0 μmol kg−1s.c.) had no, or weakly facilitatory effects on the male rat ejaculatory behaviour. The non‐selective 5‐HT1receptor antagonist (−)‐pindolol (8 μmol kg−1s.c.), did not antagonize the inhibition produced by anpirtoline.The present results demonstrate opposite effects, facilitation and inhibition, of male rat ejaculatory behaviour by stimulation of 5‐HT1Aand 5‐HT1Breceptors, respectively, suggesting that the SSRI‐induced inhibition of male ejaculatory dysfunction is due to 5‐HT1Breceptor stimulation.