| 1. |
- Edwards, A V, et al.
(författare)
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Nitric oxide and release of the peptide VIP from parasympathetic terminals in the submandibular gland of the anaesthetized cat.
- 1996
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Ingår i: Experimental physiology. - 0958-0670. ; 81:3, s. 349-59
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Tidskriftsartikel (refereegranskat)abstract
- The role of nitric oxide (NO) in mediating various submandibular responses to stimulation of the parasympathetic innervation has been investigated in anaesthetized cats, in which N omega-nitro-L-arginine methyl ester (L-NAME; 30 mg kg-1 I.A.) was used to block the synthesis of NO. L-NAME significantly reduced the vasodilator response and the flow of saliva, together with the output of salivary protein that occurred during stimulation of the chorda lingual nerve (20 Hz for 1 s at 10 s intervals), without significantly reducing the output of vasoactive intestinal peptide (VIP) from the gland. The results show that NO is implicated not only in the release of VIP, as established previously, but also in mediating its actions following release in the submandibular gland of the cat.
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| 2. |
- Sjögren, C, et al.
(författare)
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An experimental model for long-term examinations of urethral and uterine pressures in conscious dogs: effect of a highly selective compound contracting urethral smooth muscles.
- 1995
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Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 153:1, s. 201-5
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Tidskriftsartikel (refereegranskat)abstract
- An experiment model was designed for studies of urethral and uterine pressures in a conscious animal, thereby avoiding the interference of anesthesia on these responses. Dogs were trained to stand in cradles for an experimental period of 3 hours, during which urethral and uterine pressures and ECG were recorded. Substances were administered either orally or intravenously. Intravenously given phenylpropanolamine (PPA; 0.3 mg./kg.) and a newly synthetized compound S113 (0.5 mg./kg. intravenously) increased the urethral pressure by about 30 and 100%, respectively. Oral administration of PPA (3.5 mg./kg.) and S113 (6 mg./kg.) increased it by about 60 and 85%, respectively. In contrast to PPA, S113 evoked no cardiac effects. Whereas PPA had pronounced effects on uterine contractility, S113 had only minor effects. Furthermore, the responses in the experiments were stable and reproducible. This dog model seems to be useful for long-term recordings of urethral and uterine pressures.
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| 3. |
- Tobin, Gunnar, 1954, et al.
(författare)
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In vivo and in vitro effects of muscarinic receptor antagonists on contractions and release of [3H]acetylcholine in the rabbit urinary bladder.
- 1995
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Ingår i: European journal of pharmacology. - 0014-2999. ; 281:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The functional effects of muscarinic receptor antagonists were examined in vivo and in vitro on the rabbit urinary bladder. Inhibitory effects on carbachol-evoked contractions of detrusor strips were pronounced for 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; -logIC50: 8.64), p-fluoro-hexahydro-sila-diphenidol (pFHHSiD; 7.84) and atropine (8.27), while they were less pronounced for pirenzepine (6.62) and methoctramine (5.36). 4-DAMP and methoctramine increased 3H overflow from [3H]choline-labelled strips in response to electrical stimulation, contrary to pirenzepine, which decreased the overflow. Concomitant contractions were markedly reduced by 4-DAMP and by pirenzepine, but not by methoctramine. The -logIC50 estimations for atropine-sensitive electrically evoked contractions revealed methoctramine (4.85) to be less potent on nerve-evoked contractions than on carbachol-evoked contractions, in contrast to pirenzepine (7.15) and 4-DAMP (9.15). The effects of the antagonists in anaesthetized rabbits resembled those in vitro. Thus, muscarinic receptors in the rabbit urinary bladder are heterogeneous; prejunctional facilitatory (M1) and inhibitory (M2) for acetylcholine release, and postjunctional muscarinic M3 receptors mediating contractile responses.
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| 4. |
- Tobin, Gunnar, 1954
(författare)
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Muscarinic receptor subtypes in the submandibular gland and the urinary bladder of the rabbit: in vivo and in vitro functional comparisons of receptor antagonists.
- 1995
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Ingår i: Journal of autonomic pharmacology. - 0144-1795. ; 15:6, s. 451-63
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Tidskriftsartikel (refereegranskat)abstract
- 1. In pentobarbitone-anaesthetized rabbits, the inhibitory effects of muscarinic receptor antagonists with different selectivity profiles were examined on carbachol-evoked submandibular secretion and urinary bladder contractions, and on parasympathetically nerve-evoked secretion. On isolated submandibular gland fragments, the inhibitory effects of the antagonists were studied on carbachol-evoked release of potassium and on the overflow of tritium in response to electrical field stimulation. 2. In vivo, 4-DAMP equipotently inhibited simultaneously carbachol-evoked submandibular secretory and contractile responses of the urinary bladder, while pirenzepine was found to be four times as potent in inhibiting the secretory response compared with the contractile response. 3. The inhibition of carbachol-evoked salivation caused by atropine, 4-DAMP and pirenzepine was as great as their inhibition of parasympathetic nerve-evoked salivation. Methoctramine exerted less inhibitory effect on nerve-evoked salivation than on carbachol-evoked, thus seemingly causing greater presynaptic inhibition. 4. In vitro, pirenzepine was only 30 times less potent in inhibiting carbachol-evoked potassium release than 4-DAMP (pA2, 9.58 vs 8.10). Whereas atropine, 4-DAMP and pirenzepine abolished the overflow of tritium from isolated glands in response to electrical field stimulation, methoctramine increased it. 5. It is concluded that the muscarinic secretory response in the rabbit submandibular gland is exerted via both muscarinic M1 and M3 receptors, while the contractile response of the urinary bladder to muscarinic agonists is exerted via muscarinic M3 receptors. The release of acetylcholine from nerve terminals in the gland can be inhibited via M2 autoreceptors in rabbits.
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| 5. |
- Tobin, Gunnar, 1954, et al.
(författare)
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Nitric oxide in the control of submandibular gland function in the anaesthetized ferret.
- 1997
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Ingår i: Experimental physiology. - 0958-0670. ; 82:5, s. 825-36
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Tidskriftsartikel (refereegranskat)abstract
- Stimulation of parasympathetic innervation of the submandibular gland (2 or 20 Hz continuously or 20 Hz for 1 s at 10 s intervals), in the ferret, produced secretion of fluid and protein and a fall in vascular resistance. The responses following the administration of N omega-nitro-L-arginine methyl ester (L-NAME; 2 mmol kg-1 i.a.) to block the synthesis of nitric oxide (NO) were reduced, and the persisting responses were abolished (at 2 Hz continuously and 20 Hz intermittently) or further reduced (at 20 Hz continuously) by the additional administration of atropine. The output of vasoactive intestinal peptide (VIP) from the gland was not affected. Neither the secretory nor the vascular response to intra-arterial infusions of acetylcholine (1.25 nmol kg-1) was affected by L-NAME, whereas the vascular responses to both VIP (10 pmol kg-1) and pituitary adenylate cyclase-activating peptide (1-38) (PACAP) (0.5 pmol kg-1) were reduced thereby. Neither peptide evoked a fluid secretion per se. However, when infused during parasympathetic stimulation of saliva secretion, VIP increased both flow rate and the output of protein. These effects of VIP were abolished by L-NAME. The experiments were performed in the presence of sodium nitroprusside at doses (4-8 nmol min-1 kg-1 i.v.) aimed to counterbalance the systemic effects of L-NAME. The results show that, in the ferret, parasympathetic nerve activity increases submandibular blood flow, and elicits the flow of saliva and output of protein by mechanisms that involve in situ generation of NO, upon which the effects of VIP and PACAP but not acetylcholine are largely dependent.
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| 6. |
- Tobin, Gunnar, 1954, et al.
(författare)
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Prejunctional facilitatory and inhibitory modulation of parasympathetic nerve transmission in the rabbit urinary bladder.
- 1998
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Ingår i: Journal of the autonomic nervous system. - 0165-1838. ; 68:3, s. 153-6
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Tidskriftsartikel (refereegranskat)abstract
- Release of [3H]choline and muscle contraction in response to electrical field stimulation were measured from rabbit detrusor muscle strips previously loaded with [3H]choline. The importance of different stimulation frequencies (1 and 10 Hz) for activating either facilitatory or inhibitory prejunctional effects was examined in the presence of muscarinic and adrenergic (alpha2) receptor selective substances. At 1 Hz, neither [3H]choline overflow nor contraction was affected by the M1-selective receptor antagonist pirenzepine (10(-7) M), whereas overflow and contraction decreased at 10 Hz. The M1-selective receptor agonist McN-A-343 (10(-6) M) caused no significant changes except for reducing contractions at 10 Hz. The M2-selective receptor antagonist methoctramine (10(-6) M), on the other hand, increased overflow as well as contraction at both frequencies, most conspicuously at 1 Hz. Atropine (10(-7) M) caused a significant increase with respect to overflow only at 1 Hz, while quite the opposite effect occurred with respect to contractions (reduced only at 10 Hz). Clonidine (10(-6) M) induced inhibition of [3H]choline overflow at 10 Hz only, but without significantly changing contractile responses. The results show that in the rabbit urinary bladder a muscarinic autoreceptor mediated inhibition (M2) of the transmitter release dominates during low frequency stimulation and that a facilitation (M1) may be present at stimulations with higher frequencies. However, this amplification may also be influenced by alpha2-adrenoceptor mediated inhibition.
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| 7. |
- Tobin, Gunnar, 1954
(författare)
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Presynaptic muscarinic M1 and M2 receptor modulation of auriculotemporal nerve transmission in the rat.
- 1998
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Ingår i: Journal of the autonomic nervous system. - 0165-1838. ; 72:1, s. 61-71
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Tidskriftsartikel (refereegranskat)abstract
- Parotid secretory and vascular responses to electrical stimulation of the parasympathetic innervation were measured in anaesthetized rats. Stimulation was performed at 1, 10 and 40 Hz. Atropine (1.5 micromol/kg i.v.) almost abolished the secretion to stimulation of peptide depleted nerves at 40 Hz, thus confirming the existence of a pure cholinergic response. Atropine also reduced secretion by 74% during stimulation of non-depleted nerves at the same frequency. Selective blockade by the muscarinic M1 receptor antagonist pirenzepine and by the muscarinic M2 receptor antagonist methoctramine was found to occur at doses (50 nmol/kg i.v. and of 300 nmol/kg i.v., respectively) that did not inhibit the responses to exogenous acetylcholine. In the presence of methoctramine, the nerve-evoked fluid responses were increased by 200% at 1 Hz independently of the total number of impulses (10-300), suggesting that M2 receptor activation normally has an inhibitory effect on transmitter release. The magnitude of the increase was inversely related to frequency of stimulation, and changes in the secretory responses occurred at 40 Hz only when non-depleted nerves were stimulated over the longest period employed. The fluid response then increased by 35% and protein concentration by 200%. The vasodilator responses increased at 1 and 10 Hz, but not at 40 Hz. Pirenzepine reduced the secretory and vascular responses at 10 and 40 Hz but only during stimulation over short periods of time. This suggests that M1 receptor activation normally has a facilitatory effect on neurotransmitter release. During stimulation of non-depleted nerves at 10 Hz for 10 impulses, the fluid response was reduced by 29% and the protein concentration by 26%. When the peptide depleted nerves were stimulated at 10 Hz, pirenzepine also reduced the fluid response (by 43%), but not the protein concentration. It is concluded that the release of transmitter from postganglionic nerve fibres in the rat auriculotemporal nerve is modulated by presynaptic muscarinic receptors. Muscarinic M1 receptors normally facilitate cholinergic and peptidergic transmission during short, intense stimulation. On the other hand, muscarinic M2 receptors normally inhibit cholinergic transmission at low frequencies; at higher frequencies, peptidergic transmission is also inhibited, but only after some delay.
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