Muscarinic receptor subtypes in the bisected vas deferens of the rat

• 1.1. The nature of muscarinic receptor subtypes in the isolated prostatic and epididymal segments of the vas deferens of the rat were studied.
• 2.2. Presynaptic receptors were characterized in segments under neurogenic transmural stimulation; postsynaptic receptors in segments without stimulation.
• 3.3. The present work suggests that the potency of ACh required to activate muscarinic receptors is higher in the prostatic than in the epididymal segment.
• 4.4. McN-A-343 was only able to induce dose-dependent contractions in the prostatic segment.
• 5.5. The pA₂ value for 4-DAMP suggests that in the prostatic segment the postsynaptical ACh receptors seem to be pharmacologically similar to the ACh-M₃ subtype.
• 6.6. Antagonism of the presynaptic ACh receptor subtype by pirenzepine supports the evidence that these receptors belong to the ACh-M₁ subtype.

     

Cholinergic receptor agonists inhibit pirenzepine-induced dysfunction of spontaneous alternation performance in the mouse

• 1.1. The present study was designed to examine the effects of intracerebroventricular injection of several cholinergic drugs on the impairment of spontaneous alternation performance induced by the M₁-selective muscarinic receptor antagonist pirenzepine.
• 2.2. Pirenzepine (3 and 10 μg) significantly reduced spontaneous alternation performance related to working memory without producing any marked increase in total arm entries, which are considered to reflect locomotor activity.
• 3.3. Physostigmine (3.47 μg), a cholinesterase inhibitor, and McN-A-343 (20 μg), an M₁-selective muscarinic receptor agonist, significantly improved the pirenzepine (3 μg)-induced impairment of spontaneous alternation performance, although oxotremorine (0.68 μg), a nonselective muscarinic receptor agonist, showed a tendency to reverse the pirenzepine (3 μg)-induced impairment.
• 4.4. These findings suggest that the blockade of muscarinic M₁ but not M₂ receptors results in the impairment of spontaneous alternation performance associated with working memory.

     

Molecular pharmacology of V1a vasopressin receptors

• 1.1. Vasopressin, a mammalian neurohypophysial peptide hormone, has diverse physiological actions.
• 2.2. Pharmacological studies, using a range of mammalian tissues, have identified three subtypes of vasopressin receptor.
• 3.3. The V_1a subtype of vasopressin receptor is widely distributed and mediates many central and peripheral actions of vasopressin.
• 4.4. The development of subtype-selective vasopressin analogues has provided valuable tools for pharmacological and physical studies of the V_1a receptor protein.
• 5.5. Pharmacological differences indicate species heterogeneity in the characteristics of V_1a receptors and in the expression of hepatic V_1a receptors.
• 6.6. The cloning of neurohypophysial hormone receptor proteins allows structural and functional comparison of the V_1a vasopressin receptors with other G-protein-coupled receptors.

     

Adenosine selectively depresses muscarinic compared with non-muscarinic receptor mediated depolarisation of the rat superior cervical ganglion

• 1.1. A grease gap d.c. recording technique was used to measure electrophysiological responses of the isolated rat superior cervical ganglion.
• 2.2. Adenosine at 100 μM depressed depolarisations to the muscarinic agonists carbachol, muscarine and methylfurmethide. In contrast adenosine (100μM) did not alter depolarisations to 1,1-dimethyl-4-phenylpiperazinium, 2-methyl-5-hydroxytryptamine and potassium and enhanced depolarisations to 5-hydroxytryptamine and gamma-aminobutyric acid.
• 3.3. Adenosine-induced depressions of the depolarisations to carbachol, muscarine, and methylfurmethide tended to be increased in the presence of 0.3 μM methoctramine (a muscarinic receptor antagonist with slight selectivity for M₂ receptors). The increase was statistically significant (P < 0.01) for carbachol.
• 4.4. Medium containing 0.1 mM Ca²⁺ and 0.3 μM pirenzepine augmented the hyperpolarising phase of the response to carbachol. Adenosine (10–300μM) hyperpolarised ganglia and did not significantly alter the hyperpolarisation to 0.3 or 1 μM carbachol but selectively reduced the depolarisation response to 3 μM carbachol.
• 5.5. Adenosine-induced hyperpolarisations (100 μM) were enhanced when applied during depolarisations to muscarinic agonists (muscarine, pilocarpine, N-methyl-N-(1-methyl-4-pyrrolidine-2-butynyl)acetamide (BM-5)), and other M-current inhibitors, barium and eledoisin-related-peptide. Adenosine induced hyperpolarisations were not affected by d-Ala⁶-luteinizing-hormone-releasing-hormone or uridine 5′-triphosphate which produced small depolarisations.
• 6.6. It is concluded that adenosine acts selectively in opposing mechanisms of depolarisation of the rat SCG that are due to the action of muscarinic agonists (acting via M₁-receptors) and by other M-current inhibitors.

     

Prejunctional effect of quaternary derivatives of l-hyoscyamine at the rat neuromuscular junction. A structure-activity relationship study

• 1.1. The effects of phenthonium and related compounds on the spontaneous release of acetylcholine (ACh) were investigated with electrophysiological and radiolabelled techniques to correlate the prejunctional effect with their cholinolytic activities and to determine the structure-activity relationship.
• 2.2. Phenthonium and endophen are N-(4-phenyl)-phenacyl derivatives of l-hyoscyamine in “exo” and “endo” conformation, respectively. Tropol is N-(4-phenyl) phenacyl tropan-3-ol whereas ipratropium is 8-isopropyl-noratropine.
• 3.3. Only phenthonium increased the frequency of miniature endplate potentials and the resting efflux of spontaneous [³H]-ACh in rat diaphragm muscles.
• 4.4. The rank order of the antimuscarinic potency was: ipratropium > atropine > phenthonium = endophen > tropol. The rank order of the antinicotinic activity was: phenthonium = endophen > tropol > atropine > ipratropium.
• 5.5. It is concluded that the prejunctional facilitatory effect of phenthonium is associated with the N-phenyl-phenacyl group at “exo” conformation but the effect is unrelated to its cholinolytic properties.

     

Effects of oxotremorine and pilocarpine on striatal acetylcholine release as studied by brain dialysis in anesthetized rats

• 1.1. The effects of oxotremorine and pilocarpine on striatal acetylcholine (ACh) release were investigated using brain microdialysis techniques in urethan-anesthetized rats.
• 2.2. Oxotremorine (0.1 and 0.5 mg/kg, IV), a preferential M₂ agonist, dose-dependently decreased ACh release in the striatum. On the other hand, pilocarpine, at 5 mg/kg (IV), showed a tendency to decrease ACh release in the striatum but, at 7.5 and 10 mg/kg (IV), significantly enhanced release in a dose-dependent manner.
• 3.3. The effect of oxotremorine was blocked by scopolamine (0.1 mg/kg, IV) but not by pirenzepine (10 mg/kg, IV), a selective M₁ antagonist.
• 4.4. Pilocarpine (10 mg/kg, IV) enhancement of striatal ACh release was not affected by 10 mg/kg pirenzepine, but 5 mg/kg pilocarpine significantly increased ACh release in scopolamine (0.1 mg/kg) pretreated rats without affecting the release by itself.
• 5.5. These results suggest that oxotremorine-induced decrease in striatal ACh release is due to stimulation of presynaptic M₂ autoreceptor, and that the increase of striatal ACh release by pilocarpine is mediated by mechanism(s) other than effects on muscarinic ACh receptors.

     

Stimulation of angiotensin subtype 2 receptor reduces basal cGMP levels in the neointima of rat aorta after balloon injury

• 1.1. The association between the stimulation of the angiotensin subtype 2 receptor (AT2-R) and the change in tissue levels of cyclic nucleotide was assessed on neointima formation in rat aorta following aortic balloon injury.
• 2.2. Tissue levels of guanosine 3′,5′-cyclic monophosphate (cGMP) and adenosine 3′,5′-cyclic monophosphate levels (cAMP) in the injured and uninjured aorta was determined by enzyme immunoassay at baseline and again 30 s after administration of 10⁻⁷ M angiotension II.
• 3.3. Injured and uninjured aorta showed no difference in basal levels of cGMP. Angiotension II reduced the basal level of cGMP in the injured aorta only.
• 4.4. This decrease was blocked by a selective AT2-R antagonist (PD123319) and by a nonselective angiotensin II antagonist (angiotensin II antipeptide), but not by a selective angiotensin subtype 1 antagonist (CV-11974).
• 5.5. Stimulation with a selective AT2-R caused no change in the level of cAMP in the injured or uninjured aorta.
• 6.6. Results suggest that stimulation of AT2-R in proliferative neointima leads to a decreased tissue level of cGMP.

     

Characterization of the muscarinic receptor subtype(s) mediating contraction of the guinea-pig lung strip and inhibition of acetylcholine release in the guinea-pig trachea with the selective muscarinic receptor antagonist tripitramine

1. The muscarinic receptor subtypes mediating contraction of the guinea-pig lung strip and inhibition of the release of acetylcholine from cholinergic vagus nerve endings in the guinea-pig trachea in vitro have previously been characterized as M₂-like, i.e. having antagonist affinity profiles that are qualitatively similar but quantitatively dissimilar compared to cardiac M₂ receptors. The present study sought to establish definitely the identity of these receptor subtypes by using the selective muscarinic receptor antagonist, tripitramine. Guinea-pig atria and guinea-pig trachea (postjunctional contractile response) were included for reference.
2. It was found that tripitramine antagonized methacholine-induced contractions of the guinea-pig lung strip with a pK_B value of 8.76±0.05. Both the parallel shifts of the concentration-response curves and the slope of the Schild plot being not significantly different from unity (when antagonist preincubation was for 2 h) indicated the involvement of a single population of receptors in the contractile response. From the pK_B values obtained with tripitramine and a range of other selective muscarinic receptor antagonists (cf. Roffel et al., 1993), this single population of receptors can only be classified as M₂-like.
3. Tripitramine antagonized methacholine-induced negative chronotropic and inotropic responses in guinea-pig right and left atria with apparent pK_B values of 9.4–9.6. However, such values were only obtained when antagonist preincubation was relatively long and/or antagonist concentration relatively high (e.g. with 1 h at 100 or 300 nM but 3 h at 30 nM). It thus appears that low concentrations of tripitramine do not readily equilibrate with M₂ receptors in guinea-pig atria nor with M₂-like receptors in the guinea-pig lung strip.
4. Tripitramine increased electrical field stimulation-induced cholinergic twitch contractions in guinea-pig trachea in concentrations of 0.3–100 nM, by blocking prejunctional muscarinic inhibitory autoreceptors; with higher concentrations, twitch contractions were progressively diminished, as a result of blocking postjunctional M₃ receptors (apparent pK_B value 6.07±0.15). The pEC₂₀ value (−log concentration that increases twitch by 20% of maximum) was 8.29±0.08, which would suggest that M₄ receptors are involved in this response.
5. Oxotremorine-induced inhibition of the release of prelabelled [³H]-acetylcholine from guinea-pig trachea, under conditions where there is no auto-feedback, was blocked by tripitramine (2 h preincubation) with a pK_B value of 8.56±0.06. The slope of the corresponding Schild plot was not significantly different from unity, which together with the parallel shifts of the concentration-response curves indicated the involvement of a single muscarinic receptor subtype.
6. Since the pK_B value for tripitramine at prejunctional receptors in guinea-pig trachea is in between the affinities towards M₂ and M₄ receptors, correlation plots were constructed to compare the pK_B values obtained with tripitramine and a range of other selective muscarinic receptor antagonists (cf. Kilbinger et al., 1995) to reported affinities at M₁–M₄ receptors. This showed rather similar distribution patterns of the data points around the line of equality in the case of M₂ and M₄ receptor subtypes. However, the correlation coefficient was markedly better for M₂ (0.9667) than for M₄ (0.5976). Since recent evidence suggests that M₄ receptors are not expressed in cholinergic nerves from guinea-pig trachea, it is concluded that prejunctional muscarinic autoinhibitory receptors in this tissue exhibit an atypical M₂ type character, with a pharmacological profile distinct from cardiac M₂ receptors.

     

A lack of supersensitivity to opioid receptor agonists following chronic spinal opioid receptor antagonist administration in the rat

• 1.1. Male Sprague-Dawley rats were chronically tested with intrathecal (i.t.) receptor selective opioid antagonists to determine if antinociceptive supersensitivity developed to selective i.t. opioid receptor agonists.
• 2.2. A subcutaneously implanted osmotic minipump was used to deliver the μ-opioid receptor antagonist CTOP (0.3 nmol) or the b-opioid receptor antagonist naltrindole (5.5 nmol) for 7 days.
• 3.3. Following a 24 hr washout period, rats received a single i.t. dose (ED₅₀) of either DAMPGO (for CTOP-treated animals) or DPDPE (for naltrindole-treated animals) and the antinociceptive effects of the agents were tested on the tail-flick test.
• 4.4. Our findings revealed that chronic spinal treatment with selective opioid receptor antagonists did not induce an antinociceptive supersensitivity to selective opioid receptor agonists.
• 5.5. Perhaps this lack of supersensitivity is reflective of difficulties inherent to opioid receptor antagonists that do not possess negative intrinsic activity

.     

Effects of the selective 5-HT receptor agonists 8-OHDPAT and DOI on behavior and brain biogenic amines of rats

• 1.1. The behavioral responses, as well as the biogenic amines and metabolite contents in discrete brain areas were determined in male rats subcutaneously treated with a 5-HT_1A (8-OHDPAT) or 5-HT_2A (DOI) agonist at doses (0.5-2 mg/kg) sufficient to produce the typical effects of the stimulation of these brain receptor subtypes.
• 2.2. Besides the expected effects (i.e., forepaw treading, flat body posture and inhibition of 5-HT release and turnover), 8-OHDPAT displayed signs of increased dopaminergic transmission.
• 3.3. DOI increased dopamine turnover and provoked stereotypical behavior, in addition to head shakes and body twitches.
• 4.4. Moreover, DOI induced both forepaw treading and flat body posture, which are believed to be typical responses to the stimulation of brain 5-HT_1A receptors.
• 5.5. This finding cannot be explained on the basis of actual knowledge, because the affinity of DOI for 5-HT_1A receptor has been found to be very low, whereas indirect mechanisms of activation of this receptor subtype triggered by stimulation of 5-HT_2A receptor are actually unknown.

     

Role of calcium in mediating the biphasic contraction of the rabbit urinary bladder

• 1.1. The response of the urinary bladder to field stimulation is biphasic in nature consisting of an initial phasic contraction followed by a prolonged tonic phase which lasts for the duration of the stimulation.
• 2.2. The phasic response is mediated by the release of neurohumoral transmitters, primarily acetylcholine (via muscarinic receptor stimulation) and ATP (via purinergic receptor stimulation). The tonic component is mediated entirely via muscarinic receptor stimulation.
• 3.3. The present study investigates the dependence on extracellular calcium of the phasic and tonic contractile responses to field stimulation, bethanechol, and ATP. The results can be summarized as follows:
• 4.4. Field stimulation (2 and 32 Hz) and bethanechol evoke a biphasic contractile response whereas ATP evokes only a phasic response.
• 5.5. There were no significant effects of either calcium channel blockers or calcium fee EGTA medium on either spontaneous contraction or basal tension of muscle strips.
• 6.6. The calcium channel antagonists diltiazem and verapamil inhibited both the phasic and tonic responses induced by field stimulation (both 2 and 32 Hz) in a dose dependent manner.
• 7.7. For both 2 and 32 Hz stimulation, the ED₅₀s for the inhibition of the tonic phases of the responses to field stimulation were significantly lower than the ED₅₀s for the inhibition of the phasic responses.
• 8.8. The tonic phase of the responses to field stimulation were inhibited to a significantly greater degree than the phasic responses by incubation in calcium-free medium containing EGTA.
• 9.9. Both the phasic and tonic components of the response to bethanechol stimulation were inhibited equally, and followed a similar time course as the tonic component of field stimulation.
• 10.10. The response to ATP was relatively insensitive to calcium depletion.
• 11.11. In summary, the tonic response to field stimulation (purely cholinergic) is significantly more dependent on extracellular calcium than is the phasic response (cholinergic + purinergic).

     

Neuromuscular facilitation induced by muscarinic antagonists in the rat isolated diaphragm

• 1.1. Atropine (EC₅₀ = 87 μM), pirenzepine (447 μM), and AF-DX 116 (95.5 μM), but not 4-DAMP (at concentrations of up to 110 μM), produced neuromuscular facilitation and antagonized the oxotremorine-induced neuromuscular blockade in the rat isolated diaphragm.
• 2.2. Atropine, pirenzepine, and AF-DX 116 did not change the responses of curarized diaphragms to direct stimulation, or the twitch tension produced by retrograde injection of acetylcholine.
• 3.3. These results indicate that neuromuscular facilitation induced by muscarinic antagonists may depend on drug interaction with the M2 subtype of muscarinic autoreceptors to increase acetylcholine output in the neuromuscular junction.

     

Effects of selective dopamine receptor compounds on single,spontaneously-active neostriatal neurons

• 1.1. The effects of selective dopamine receptor compounds on the spontaneous activity of single neostriatal neurons were examined extracellularly.
• 2.2. Intravenous administration of quinpirole, the D₂ agonist, elicited a dose-dependent depression in discharge rate.
• 3.3. Quinpirole-evoked depression was reversed by the D₂ antagonist eticlopride, but not the D₁ antagonist SCH 23390.
• 4.4. The partial D₁ agonist, SKF 38393 induced depression and excitation in equal proportion.
• 5.5. A dose of 0.25 mg/kg SCH 23390 blocked SKF 38393-induced depression but not excitation.
• 6.6. SKF 38393-induced excitation was antagonized by eticlopride and in some cases by a higher dose of SCH 23390.

     

Carbachol-induced desensitization of rat basophilic leukemia (RBL-2H3) cells transfected with human m3 muscarinic acetylcholine receptors

• 1.1. Carbachol-induced homologous desensitization of the secretory response was investigated by transfecting RBL-2H3 cells with cDNA encoding the human m3 muscarinic acetylcholine receptor (RBL-m3).
• 2.2. Exposure of RBL-m3 cells to 100 μM carbachol for 30 min in Ca²⁺-free medium inhibited the secretion induced by the subsequent addition of 10 μM carbachol plus Ca²⁺.
• 3.3. Desensitized cells bound [³H]quinuclidinyl benzilate with a similar B_max and K_d to those of control cells.
• 4.4. The carbachol-induced transient increase in levels of inositol 1,4,5-trisphosphate was not changed by desensitization.
• 5.5. Homologous desensitization persisted when desensitized cells were permeabilized with Staphylococcal α-toxin.

     

β-adrenergic receptor and platelet inhibitory activities of a new series of trimetoquinol and related benzazepine analogs

• 1.1. A series of dimethoxy and methylenedioxy analogs of trimetoquinol (TMQ) and structurally related 7-membered ring benzazepines (BA) were evaluated for their pharmacological effects in β-adrenergic (atria, trachea) and thromboxane A₂/prostaglandin H₂ receptor systems (aorta, platelets).
• 2.2. Results show that both the 6,7-dihydroxy (catechol) moiety of trimetoquinol and an intact tetra-hydroisoquinoline nucleus are essential for maintaining potent β-stimulating and antithromboxane A₂ activities.
• 3.3. By contrast, ring enlargement, as in the BA analogs, or masking of the catechol with dimethoxy or methylenedioxy functional groups enhanced the potency of inhibitors on thromboxane A₂-independent activation of human platelets induced by bacterial phospholipase C (PLC).
• 4.4. The selective blockade of this pathway by these compounds suggests that they may represent a new and novel class of antiplatelet drugs.

     

Breastmilk can mediate chemical imprinting. Benzpyrene exposure during lactation reduces the thymic glucocorticoid receptor density of the offspring

• 1.1. Prolonged benzpyrene treatment during lactation reduced the number of glucocorticoid receptors of offspring in adulthood significantly without altering the receptor affinity.
• 2.2. Dexamethasone treatment identical to benzpyrene exposure had no effect either on receptor number or affinity.
• 3.3. The results of the present investigations draw attention to the possible way of receptor alteration via breastmilk.

     

Fluoroaluminate induces rapid release of endothelin-1 in the isolated perfused arterial and venous vessels of the rat mesentery

• 1.1. Endothelin-1 (ET-1) production from endothelial cells is generally believed to be a process that happens over the course of hours.
• 2.2. When fluoroaluminate (AIF₄⁻) was infused in the isolated perfused arterial and venous vessels of the rat mesentery there was an increase in perfusion pressure on both sides.
• 3.3. Treatment of mesentery with the endothelin receptor antagonists FR 139317 (ET_A receptor selective) or PD 145065 (ET_A-ET_B receptor nonselective) caused inhibition on both the arterial and venous sides, suggesting that response is mediated predominantly by endothelin-1 through ET_A receptors.
• 4.4. Endothelial denudation attenuated changes in perfusion pressure of mesenteric circulation generated by fluoroaluminate, but not those caused by exogenously added PGF_2α.
• 5.5. Our data demonstrate that there is an immediate release of endothelin-1 following fluoroaluminate infusion which could be partially mediated by activation of phospholipase C.

     

Effects of NIK-247 and Tacrine on Muscarinic Receptor Subtypes in Rats

• 1.The purpose of this study was to compare the effect of NIK-247 on muscarinic receptor subtypes with that of tacrine (THA) in rats.
• 2.NIK-247 and tacrine dose dependently inhibited the binding of [³H]pirenzepine (M₁), [³H]AF-DX 384 (M₂), and [³H]4-DAMP (M₃). The IC₅₀ values for NIK-247 were 4.4×10⁻⁶ M, 1.1×10⁻⁵ M, and 1.5×10⁻⁵ M, respectively, whereas those for tacrine were 5.8×10⁻⁷ M, 2.0×10⁻⁶ M, and 5.8×10⁻⁶ M, respectively.
• 3.Gpp[NH]p, a GTP analogue, slightly shifted the curve of displacement of [³H]AF-DX 384 binding for NIK-247 to the right. However, Gpp[NH]p did not shift the curve of displacement of [³H]pirenzepine and [³H]4-DAMP binding to the right.
• 4.NIK-247 moderately decreased the rate of beating in right atrial preparations, but did not decrease it below 50% of control level.
• 5.These findings indicate that NIK-247 is an M₁ antagonist, M₂ partial agonist, and M₃ antagonist.

     

Prostaglandin E2 suppression of acetylcholine release from parasympathetic nerves innervating guinea-pig trachea by interacting with prostanoid receptors of the EP3-subtype

1. We have demonstrated recently that exogenous prostaglandin E₂ (PGE₂) inhibits electrical field stimulation (EFS)-induced acetylcholine (ACh) release from parasympathetic nerve terminals innervating guinea-pig trachea. In the present study, we have attempted to characterize the pre-junctional prostanoid receptor(s) responsible for the inhibitory action of PGE₂ and to assess whether other prostanoids modulate, at a prejunctional level, cholinergic neurotransmission in guinea-pig trachea. To this end, we have investigated the effect of a range of both natural and synthetic prostanoid agonists and antagonists on EFS-evoked [³H]-ACh release.
2. In epithelium-denuded tracheal strips pretreated with indomethacin (10 μM), PGE₂ (0.1 nM–1 μM) inhibited EFS-evoked [³H]-ACh release in a concentration-dependent manner with an EC₅₀ and maximal effect of 7.62 nM and 74% inhibition, respectively. Cicaprost, an IP-receptor agonist, PGF_2α and the stable thromboxane mimetic, U46619 (each at 1 μM), also inhibited [³H]-ACh release by 48%, 41% and 35%, respectively. PGD₂ (1 μM) had no significant effect on [³H]-ACh release.
3. The selective TP-receptor antagonist, ICI 192,605 (0.1 μM), completely reversed the inhibition of cholinergic neurotransmission induced by U-46619, but had no significant effect on similar responses effected by PGE₂ and PGF_2α.
4. A number of EP-receptor agonists mimicked the ability of PGE₂ to inhibit [³H]-ACh release with a rank order of potency: GR63799X (EP₃-selective)>PGE₂>M&B 28,767 (EP₃ selective)>17-phenyl-ω-trinor PGE₂ (EP₁-selective). The EP₂-selective agonist, AH 13205 (1 μM), did not affect EFS-induced [³H]-ACh release.
5. AH6809 (10 μM), at a concentration 10 to 100 times greater than its pA₂ at DP-, EP₁- and EP₂-receptors, failed to reverse the inhibitory effect of PGE₂ or 17-phenyl-ω-trinor PGE₂ on [³H]-ACh release.
6. These results suggest that PGE₂ inhibits [³H]-ACh release from parasympathetic nerves supplying guinea-pig trachea via an interaction with prejunctional prostanoid receptors of the EP₃-receptor subtype. Evidence for inhibitory prejunctional TP- and, possibly, IP-receptors was also obtained although these receptors may play only a minor role in suppressing [³H]-ACh release when compared to receptors of the EP₃-subtype. However, the relative importance of the different receptors will depend not only on the sensitivity of guinea-pig trachea to prostanoids but on the nature of the endogenous ligands released locally that have activity on parasympathetic nerves.

     

Central and peripheral dopamine D1/DA1 receptor modulation of gastric secretion and experimental gastric mucosal injury

• 1.1. Dopamine D₁ (central)/DA₁ (peripheral) receptors are believed to influence gastrointestinal function and pathology.
• 2.2. When given i.c.v. or i.p., an agonist (SKF38393) and an antagonist (SCH23390) of this DA receptor subtype inhibit and enhance, respectively, gastric secretion and gastric mucosal injury.
• 3.3. When given both i.c.v. and i.p., their respective effects in the gut were amplified.
• 4.4. Antagonist or agonist given i.p., blocked the corresponding protective and worsening effect of the agonist or antagonist given i.c.v.
• 5.5. Both central and peripheral D₁/DA₁ receptors modulate gastric function and response to injury.