Release of acetylcholine mediated by cholecystokinin receptor from the guinea pig sphincter of Oddi

Mechanisms involved in the action of cholecystokinin octapeptide (CCK-8) on the isolated circular muscle of the guinea pig sphincter of Oddi were investigated. CCK-8 (10(-9) to 10(-6) M) caused a concentration-dependent contraction of the sphincter. Angiotensin II, bethanechol and serotonin also contracted this tissue. CCK-8 exerted the most potent effect. However, bradykinin, porcine motilin and norepinephrine failed to elicit any contraction. The CCK-8-induced contraction was inhibited by about 60% by atropine (3 X 10(-7) M) or tetrodotoxin (3 X 10(-7) M) but was not affected by hexamethonium (3 X 10(-5) to 10(-4) M) or phentolamine (3 X 10(-6) to 10(-5) M). Proglumide (3 X 10(-4) to 3 X 10(-3) M), a derivative of glutaramic acid, inhibited competitively the contraction by CCK-8. However, proglumide influenced neither the electrically elicited twitch contraction nor the bethanechol-induced contraction. CCK-8 evoked a concentration-related release of [3H]acetylcholine (ACh) from previously labeled stores. The CCK-8-evoked release of [3H]ACh was eliminated by tetrodotoxin and was inhibited, in a concentration-dependent manner, by proglumide. These results suggest that the contractile response to CCK-8 of the guinea pig sphincter of Oddi consists of a direct effect on the smooth muscle and an indirect effect mediated by ACh release from postganglionic parasympathetic neurons.     

Neuromodulatory effects of atrial natriuretic peptides correlate with an inhibition of adenylate cyclase but not an activation of guanylate cyclase.

We reported previously that atrial natriuretic factor (ANF) and the ANF clearance receptor binding peptide, C-ANF(4-23)-NH2 (C-ANF), inhibit catecholamine (CA) release from rat, nerve growth factor-treated pheochromocytoma cells (PC12 cells) by a guanylate cyclase independent mechanism. This mechanism is most likely a pertussis toxin (PTX)-sensitive inhibition of adenylate cyclase. This study examines the role of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), in mediating atrial natriuretic factor effects on depolarization-induced CA release from PC12 cells. The following evidence supports the hypothesis that the neuromodulatory action of atrial peptides is independent of increases in cGMP: 1) ANF does not potentiate the inhibitory effect of C-ANF on CA release or cAMP generation but still elevates cGMP concentrations in the presence of C-ANF; 2) the neuromodulatory effects of ANF and C-ANF are blocked or reversed by a membrane permeable analog of cAMP, dibutyryl cAMP; 3) ANF and C-ANF attenuate CA release in the presence of a maximally effective concentration of dibutyryl cGMP; 4) the inhibitory effect of dibutyryl cGMP is PTX-insensitive whereas the atrial peptide effect is blocked by PTX-pretreatment; and 5) dibutyryl cGMP is without effect on adenylate cyclase. These data are consistent with the hypothesis that ANF and C-ANF act via the ANF clearance (R2) receptor to suppress adenylate cyclase activity and neurotransmission.     

Serotonin induces constriction and relaxation of the guinea pig airway

The response of guinea pig trachea to 5-hydroxytryptamine (serotonin; 5-HT) was investigated by studying tracheal strips suspended in organ chambers for isometric tension measurements. Serotonin concentrations of 0.1 to 10 microM produced concentration-dependent contractions, whereas at higher concentrations (10-300 microM) the agonist caused concentration-dependent relaxations. The 5-HT2 antagonist ketanserin shifted the bimodal 5-HT response-curve to the right (pA2 for ketanserin was 8.98). The 5-HT1A agonist, (+)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide and 5-HT3 antagonist, ICS 205930 (3-tropanyl-indole-3-carboxylate) had no effect on the 5-HT-response curve. Incubation with atropine resulted in a depression of the maximal contractility and an increase in the EC50 without changing the bimodal nature of the concentration-response curve. Hexamethonium was able to block the atropine effect without significantly affecting the 5-HT concentration-response curve. Neither the constriction nor the relaxation was altered by propranolol, chlorpheniramine or capsaicin pretreatment. Histamine and carbachol preconstricted airways were also relaxed by 5-HT in a concentration-dependent fashion and this relaxation was antagonized by ketanserin (pKb for ketanserin in histamine preconstricted airways was 9.4). Epithelial denudation did not inhibit the 5-HT-induced relaxation. 5-HT stimulated inositol-monophosphate production which also exhibited a bimodal response and correlated well with the functional response. The above findings suggest that 5-HT causes both constriction and relaxation of the guinea pig airway, and that both responses are antagonized by a 5-HT2 receptor blocker. In addition, part of the constrictor response of 5-HT is mediated through a cholinergic preganglionic pathway. Finally, inositol-monophosphate production induced by 5-HT correlates with the functional response.     

Characterisation of left ventricular relaxation in the isolated guinea pig heart

The time constant of left ventricular pressure fall, τ, has frequently been used as a measure of myocardial relaxation in the blood-perfused, ejecting heart. The aim of the present study was to characterise τ in relation to β-adrenergic activation, coronary perfusion pressure and flow as well as cardiac oxygen supply and demand in the isolated, isovolumically beating heart. Therefore, τ was analysed from digitised left ventricular pressure data in a total of 23 guinea pig hearts perfused with saline at constant pressure (60 cmH₂O). The coronary venous adenosine concentration ([ADO]) served as an index of myocardial oxygenation. Isoprenaline (0.4–3.2 nmol l⁻¹) decreased and propranolol (3–9 μmol l⁻¹) increased τ dose-dependently (linear regression τ vs lg ([isoprenaline]),r=0.74; τ vs. lg([propranolol]),r=0.66, bothP<0.05). During graded reductions in cardiac oxygen supply from 96.1±12.6(SEM) to 44.4±4.4 μl min⁻¹ g⁻¹, τ was prolonged from 61.5±12.7 to 109.9±22.6 ms while left ventricular developed pressure (LVDP) decreased from 90.7±7.2 to 40.7±5.1 mmHg. In parallel, [ADO] increased from 23.7±9.1 to 58.0±19.1 pmol ml⁻¹ (P<0.05). Increasing oxygen supply to 165.4±32.4 μl min⁻¹ g⁻¹ augmented LVDP to 102.7±7.3 mmHg but did not change τ or [ADO]. There was a dual response of τ to changes in cardiac oxygen supply or demand. As long as oxygen supply and demand matched, τ remained constant. However, when the oxygen supply was less than 100 μl min⁻¹g⁻¹, left ventricular relaxation was prolonged in parallel to the reduction in oxygen supply. In addition, a close relationship was observed between [ADO] as an indicator of myocardial oxygenation and τ (Spearman correlation,r=0.99,P<0.005). We conclude that the time constant of left ventricular pressure fall, τ, sensitively reflects myocardial relaxation in the isolated, isovolumically beating guinea pig heart. Moreover, in this model left ventricular relaxation is not influenced by alterations in coronary perfusion pressure or flow as long as cardiac oxygen demand is matched by an adequate supply. Rather, relaxation is strictly coupled to myocardial oxygenation as reflected by coronary venous adenosine concentrations.     

雌性激素对妊娠豚鼠胆囊运动功能影响的实验研究

目的:探讨妊娠情况下雌性激素对豚鼠胆囊运动功能的影响及对胆囊结石形成的作用。方法:60只雌性豚鼠随机分为实验组(40只)和对照组(20只),实验组建立妊娠豚鼠动物模型,分为妊娠30d组和妊娠60d组,采用化学发光法和酶联亲和抗体组织化学法分别进行血清雌二醇(E2)、孕酮(Pg)浓度检测及胆囊组织雌激素受体(E R)、孕激素受体(PR)的检测,同时测量各组豚鼠胆囊空腹体积(FV),胆囊空腹胆汁量(FB)的变化,并观察胆囊结石形成情况。结果:妊娠60d组豚鼠有3只形成胆囊结石,妊娠豚鼠血清E2、Pg含量,胆囊组织E R、PR阳性表达率均明显高于非孕豚鼠(P<0.001),且随妊娠期进展而呈逐渐升高趋势。妊娠60d组豚鼠FV及FB明显大于妊娠30d组和对照组(P<0.001)。结论:妊娠期血清E2和Pg含量显著升高,诱发胆囊运动功能下降,胆囊胆汁淤积,是妊娠期胆囊结石形成的重要原因。     

Pharmacological evidence for distinct muscarinic receptor subtypes coupled to the inhibition of adenylate cyclase and to the increased generation of inositol phosphates in the guinea pig myometrium

In the guinea pig myometrium, muscarinic receptor activation leads to contraction and elicits two biochemical responses viz. an increased formation of inositol phosphates (via a guanine nucleotide regulatory protein, distinct from the stimulatory and inhibitory G proteins of the adenylate cyclase system and a decreased synthesis of cyclic AMP involving inhibitory G protein activation. We now describe two major differences in the effects of muscarinic agonists. First, the greater potency of carbachol in inhibiting cyclic AMP formation (EC50 = 8 nM) than in stimulating the accumulation of inositol phosphates and tension (EC50 = 15 and 2 microM, respectively). Second, carbachol, oxotremorine and pilocarpine were equally effective in eliciting cyclic AMP inhibition but the order of potency for inositol phosphate formation was carbachol greater than oxotremorine and pilocarpine was without effect. The partial agonists, pilocarpine and oxotremorine, inhibited carbachol-mediated inositol phosphate formation. Pirenzepine, selective for muscarinic M1 receptor subtype, displayed a low affinity for antagonizing cyclic AMP inhibition, inositol phosphate generation and tension due to carbachol (Ki = 286, 92 and 110 nM, respectively). AF-DX116 (11-[( 2-[(diethylamino)methyl]-1- piperidinyl]acetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine- 6-one), selective for cardiac M2 receptors blocked cyclic AMP inhibition with high affinity (Ki = 1.14 nM) while it antagonized inositol phosphate formation with low affinity (Ki = 346 nM). Both high (Ki = 1 nM) and low (Ki = 100 nM) affinities were displayed by AF-DX116 in antagonizing contractions due to carbachol (24 and 76% inhibition, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lithium decreased endothelium‐mediated,but not nonadrenergic noncholinergic,relaxation of guinea pig corpus cavernosum in vitro: a role for nitrergic system

Lithium causes erectile dysfunction in patients but its mechanism is yet unknown. The aim of our study was to verify the effect of acute lithium administration on the nonadrenergic noncholinergic (NANC)‐ and endothelium‐mediated relaxation of guinea pig isolated corpus cavernosum. Although lithium (0.5, 1, and 5 mm ) had no effect on the neurogenic relaxations, it significantly (P < 0.001) attenuated the relaxant responses to acetylcholine in a concentration‐dependent manner. Combination of low concentration of lithium (0.5 mm ) with either 0.1 or 1 μm l ‐NAME significantly (P < 0.001) reduced the endothelium‐mediated relaxation. Although the Nitric oxide (NO) precursor l ‐arginine at 1 mm did not alter the relaxant responses to acetylcholine in control strips, it improved the inhibition by lithium (1 mm ) of relaxant responses to acetylcholine. Sodium nitroprusside (SNP; 10 nm –1 mm ) produced similar concentration‐dependent relaxations in both groups. Our experiments indicated that lithium can result in impairment of the NO‐mediated endothelium‐dependent but not NANC relaxation of guinea pig corpus cavernosum.     

Neural activation of opioid mechanisms in guinea pig ileum by excitatory peptides

The opioid antagonist naloxone added after contractions induced by excitatory peptides on the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum evoked a contracture with intensity dependent on the concentration of the antagonist and on the interval of time that elapsed after the cessation of the excitation induced by the peptides. A direct relationship was found between the component of the peptide-induced contraction that appeared to be neurally mediated and the magnitude of the subsequent contracture induced by naloxone. Moreover, the opioid agonist FK 33-824 decreased the contractile effect of the excitatory peptides and also increased the height of the naloxone-induced contractures. That effect was particularly evident when the higher doses of the peptides were studied. In the presence of atropine naloxone elicited small contractures when added after peptides with primarily neural actions, including corticotropin-releasing factor, neurotensin and cholecystokinin octapeptide 26-33 sulfated form. The naloxone-induced contracture appears to be mediated mainly by the release of acetylcholine, and to a minor extent by another spasmogenic substance from the myenteric plexus. It is concluded that endogenous opioids modulate, i.e., inhibit the release of those excitatory endogenous transmitters triggered by the effect of excitatory peptides upon the myenteric plexus.     

Transgene expression in the guinea pig cochlea mediated by a lentivirus-derived gene transfer vector.

The utility of lentivirus as a gene delivery vector in the cochlea was evaluated in vitro and in vivo. Lentivirus transduction was assessed through expression analysis of a reporter gene, green fluorescent protein (GFP), integrated within the viral genome. In vitro characterization of lentivirus-GFP was assessed by infection of explants from cochleas of neonatal rat. The lentiviral vector transduced both spiral ganglion neurons (SGNs) and glial cells. In vivo characterization of lentivirus-GFP was assessed by directly infusing the vector into the guinea pig cochlea via an osmotic minipump. Sections of lentivirus-infused cochlea revealed a highly restricted fluorescence pattern limited to the periphery of the perilymphatic space. Transduction of SGNs and glial cells by lentivirus in vitro but not in vivo suggests limited dissemination of the viral vector from the perilymphatic space. The cellular and tissue architecture of the lentivirus-infused cochlea was intact and free of inflammation. Restricted transduction of cell types confined to the periphery of the perilymphatic space by the lentivirus is ideal for stable production of gene products secreted into the perilymph.     

Activation of myocardial adenyl cyclase by histamine in guinea pig, cat, and human heart

Histamine has positive inotropic and chronotropic effects on the heart which are not abolished by beta adrenergic-blocking agents. Since the positive inotropic and chronotropic effects of other hormones on the heart are thought to be mediated by cyclic 3',5'-AMP, we examined the effect of histamine on adenyl cyclase in particulate preparations of guinea pig, cat, and human myocardium. Histamine at the peak of its dose-response curve, 3 x 10(-4)moles/liter, produced approximately a 300% increase in cyclic 3',5'-AMP accumulation in the guinea pig, 60% in the cat, and 90% in the human heart particles. Half-maximal activity for the histamine mediated activation of adenyl cyclase in the guinea pig was 9 x 10(-6)moles/liter, almost identical with that observed for norepinephrine in the same preparation. DL-Propranolol, 1 x 10(-5)moles/liter, did not abolish the activation of adenyl cyclase produced by histamine but did abolish the activation produced by norepinephrine. In contrast, diphenhydramine hydrochloride, Benadryl, 8 x 10(-5)moles/liter, abolished the activation of adenyl cyclase by histamine but not that produced by norepinephrine. These data suggest that there are at least two receptor sites in guinea pig heart mediating the activation of adenyl cyclase, one responsive to histamine, the other to norepinephrine. In addition, combined maximal doses of histamine and norepinephrine produced completely additive effects on the activation of adenyl cyclase, which suggests that at least two separate adenyl cyclase systems are present in the heart, each responsive to one of these hormones. However, definitive proof would require physical separation of the two enzymes.     

Potentiation of nonadrenergic neural relaxation in guinea pig airways by a cyclic cAMP phosphodiesterase inhibitor

We have studied the effect of phosphodiesterase inhibitors on relaxation of guinea pig tracheal smooth muscle in an attempt to elucidate the role of cyclic nucleotides in relaxation to stimulation of inhibitory nonadrenergic noncholinergic (i-NANC) nerves. SK&F 94120 (1-10 microM) potentiated relaxation induced by isoproterenol, vasoactive intestinal peptide (VIP) and electrical field stimulation (EFS) in the presence of atropine and propranolol but had no effect on relaxation induced by sodium nitroprusside. Zaprinast (3-30 microM) potentiated relaxation induced by sodium nitroprusside but not by isoproterenol or VIP. A small potentiation of relaxation to EFS was induced by 30 microM zaprinast but not by lower concentrations. Tetrodotoxin attenuated relaxations induced by EFS suggesting that they are at least partly neurogenic in origin. SK&F 94120 and zaprinast had no effect of tetrodotoxin-resistant relaxation to EFS. The guanylate cyclase inhibitor had no effect on EFS-induced relaxation. These findings suggest that cyclic AMP may mediate relaxation of guinea pig tracheal smooth muscle in response to stimulation of i-NANC nerves, and are in agreement with the view that VIP may be the neurotransmitter released by i-NANC nerves in this tissue.     

Inhibition of guinea pig ileum contractions mediated by a class of histamine receptor resembling the H3 subtype

Segments of guinea pig ileum were isolated and placed on coaxial electrodes in organ baths filled with oxygenated Krebs' solution at 37 degrees C. Twitch responses were produced with rectangular-wave stimuli (0.5 msec; 10 Hz; 4.8-12 V) delivered in 1-sec trains every 10 sec. After addition of pyrilamine to block H1-mediated contractions, histamine and N alpha-methylhistamine (NMH) inhibited the twitch responses with EC50 values of 64 and 1.7 nM, respectively. In contrast, there was no difference in potency between histamine and NMH at contractile H1 receptors in ileum longitudinal muscle or at chronotropic H2 receptors in the atria. Impromidine blocked the inhibitory effect of NMH in a competitive manner with a KB value of 26 nM, whereas inhibition caused by gamma-aminobutyric acid or by adenosine remained unaffected by impromidine. At concentrations that completely prevented the electrically induced twitch, NMH did not alter contractions produced by exogenous acetylcholine. Inhibitory responses to NMH were unaffected by cimetidine, hexamethonium, combined alpha and beta adrenergic receptor blockade, naloxone, 8-phenyltheophylline or gamma-aminobutyric acid receptor desensitization. These data support the presence of inhibitory histamine receptors in the ileum that are pharmacologically similar to the presynaptic H3 autoreceptors found in rat cortex. The distribution of H3 receptors, therefore, may not be confined to the central nervous system and their function, as with alpha-2 adrenergic sites, may not be limited to that of an autoreceptor.     

Effect of different ozone concentrations on the neurogenic contraction and relaxation of guinea pig airways

Summary— Prejunctional and postjunctional effects of several ozone (O₃) concentrations, including those found in highly polluted cities, were evaluated in guinea pig airways. Animals bred in O₃-free conditions were exposed to air or O₃ (0.3, 0.6 or 1.2 ppm) during 4 h, and studied 16–18 h later. Tracheal and bronchial rings were studied in organ baths. Electrical field stimulation (EFS) (100 V, 2 ms, 10 s) was given at increasing frequencies (0.25–16 Hz). Some tissues received atropine (2 μM) and/or propranolol (10 μM). Concentration-response curves to carbachol, isoproterenol, nitroprusside, and substance P were constructed. In tracheas, almost all O₃ concentrations decreased the relaxation at low EFS frequencies, but had no effect on the propranolol-resistant (i-NANC) relaxation, suggesting that only adrenergic relaxation was affected. This was a prejunctional effect, since O₃ did not modify the responses to isoproterenol. Relaxation induced by a nitric oxide (NO) donor, nitroprusside, was not affected by O₃, which agrees with the lack of O₃-effect on i-NANC system. O₃ did not modify the EFS-induced e-NANC contraction in atropine-treated bronchi, nor the contraction caused by exogenous substance P. By contrast, in bronchi without atropine, 1.2 ppm O₃ increased the e-NANC contraction induced by the highest EFS (16 Hz). O₃ increased the maximum responses to carbachol in tracheas (1.2 ppm) and bronchi (0.6 and 1.2 ppm). In conclusion, we found that: a) O₃ decreased adrenergic relaxation in guinea pig tracheas at low EFS frequencies through a prejunctional alteration; b) O₃ did not modify the i-NANC relaxation in tracheas, at least the NO-mediated; c) O₃ added a cholinergic component to the bronchial slow-phase (e-NANC) contraction evoked by EFS; and d) O₃ enhanced the cholinergic responses in trachea and bronchi by a postjunctional mechanism.     

Potentiation of morphine analgesia by D-amphetamine is mediated by norepinephrine and not dopamine

Morphine will raise the threshold for escape from aversive electrical stimulation delivered to the mesencephalic reticular formation and this effect is potentiated by D-amphetamine. In order to study the roles which dopamine and norepinephrine play in modulating opiate analgesia, the effects of amfonelic acid, an indirect dopamine agonist, and nisoxetine, a selective norepinephrine reuptake blocker, were determined alone and in combination with morphine using this supraspinal model of analgesia. Amfonelic acid alone produced hyperalgesia and completely antagonized the analgesic effect of morphine. Nisoxetine had no effect by itself, however, it potentiated the analgesic effect of morphine when the two drugs were administered concomitantly. These findings suggest that norepinephrine and not dopamine plays a predominant role in the potentiation of opiate analgesia by D-amphetamine.     

Cholecystokinin, but not gastrin, induces gamma-aminobutyric acid release from myenteric neurons of the guinea pig ileum

Effects of cholecystokinin (CCK) and gastrin on the release of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) were examined in the longitudinal muscle with myenteric plexus (LM-MP) preparations of the guinea pig small intestine. CCK and gastrin induced the Ca++-dependent and tetrodotoxin-sensitive release of [3H]ACh from the LM-MP preparations preloaded with [3H]choline. Proglumide, but not scopolamine, hexamethonium and [D-Pro2,D-Trp7,9]substance P inhibited the release of [3H]ACh induced by CCK and gastrin. The desensitization to CCK and gastrin was observed with a 30-min exposure of the preparation to CCK and gastrin, respectively, and the cross-desensitization to peptides was not observed, thereby indicating that these peptides induce the release of ACh mainly via respective receptors. Bicuculline which inhibited completely the release of [3H]ACh induced by GABA inhibited the release of [3H]ACh induced by CCK but not by gastrin by 42.3 +/- 4.22%. CCK, but not gastrin, produced the Ca++-dependent and tetrodotoxin-sensitive release of endogenous GABA and [3H]GABA from LM-MP preparations preloaded with [3H]GABA. The release of [3H]GABA induced by CCK was antagonized by proglumide, but not by scopolamine, hexamethonium and [D-Pro2,D-Trp7,9]substance P. These results provide evidence that the GABAergic neuron is stimulated by CCK, but not by gastrin and stimulates the cholinergic neuron.     

Release of N-[3H]methylscopolamine from isolated guinea pig atria is controlled by diffusion and rebinding

This study attempts to analyze the inter-relationship between the slow fading of muscarinic antagonist action observed in isolated tissue preparations upon washout and the dissociation kinetics at the receptor level. Isolated guinea pig left atria stimulated electrically at 3 Hz were equilibrated with N-[3H]methylscopolamine ([3H]NMS) and the time course of release of [3H]NMS was studied. In parallel experiments, the fading of the antimuscarinic action of NMS was monitored by repeated determinations of the negative inotropic effect of oxotremorine. In comparison, the dissociation of [3H]NMS from muscarinic receptors was recorded in a membrane suspension of guinea pig right atria. Having been equilibrated at 10(-8) M [3H]NMS, the atria released [3H]NMS extremely slowly, when transferred into a drug-free washout bath: not even half of the initially bound [3H]NMS was lost within 3 hr. With a corresponding time course, 10(-8) M oxotremorine regained its negative inotropic action. In contrast, when 10(-4) M unlabeled NMS was present in the washout bath, it took only 5 min for the [3H]NMS binding to fall by 50%. Similarly, in a membrane-suspension of guinea pig right atria, the half-life time of the [3H]NMS receptor complexes amounted to about 5 min. It is concluded that the dissociation of NMS from its receptor sites proceeds with a half-life time of 5 min in intact atria as well as in the cardiac membrane suspension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethanol causes neurogenic vasodilation by TRPV1 activation and CGRP release in the trigeminovascular system of the guinea pig

Ethanol stimulating transient receptor potential vanilloid 1 (TRPV1) on primary sensory neurons promotes neurogenic inflammation, including calcitonin gene-related peptide (CGRP)-mediated coronary dilation. Alcoholic beverages trigger migraine attacks and activation of trigeminal neurons plays a role in migraine. We have investigated in guinea pigs whether ethanol by TRPV1 stimulation causes neurogenic inflammation in the trigeminovascular system. Ethanol-evoked release of neuropeptides from slices of dura mater was abolished by Ca²⁺ removal, capsaicin pretreatment and the TRPV1 antagonist, capsazepine. Intragastric ethanol increased plasma extravasation in dura mater, an effect abolished by capsazepine and the NK1 receptor antagonist, SR140333, and caused vasodilation around the middle meningeal artery, an effect abolished by capsazepine and the CGRP receptor antagonist, BIBN4096BS. Vasodilation of meningeal vessels by TRPV1 activation and CGRP release may be relevant to the mechanism by which alcohol ingestion triggers migraine attacks.     

Primary visual cortex activation on the path of apparent motion is mediated by feedback from hMT+/V5

Apparent motion (AM) is the illusory perception of real motion created when two spatially distinct stationary visual objects are presented in alternating sequence. In common with many other illusory percepts, activation during AM can be identified in unstimulated regions of V1 representing the illusory motion path. However, little is known about the mechanisms underlying such activation and its relationship with motion-sensitive area hMT+/V5. Using fMRI and a novel AM stimulus, we replicated previous findings showing a correlate of the perceived AM path in V1. To more closely characterize the mechanisms underlying these activations, we performed analyses of effective connectivity and found that the AM-induced activations on the illusory AM path were associated with enhanced feedback (but not feedforward) connectivity from hMT+/V5. These findings provide for the first time evidence for the involvement of cortico-cortical coupling in generating an illusory percept of AM. They therefore emphasize the role of recurrent processing between visual cortical areas in human perceptual awareness.