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Characterization of Prejunctional Muscarinic Receptors: Effects on the Release of VIP and Functional Responses and Receptor Expression in the Ovine Submandibular Gland.

Ryberg AT, Soukup O, Tobin G - Adv Pharmacol Sci (2009)

Bottom Line: While metchoctramine increased the output of protein, pirenzepine inhibited flow of saliva and increased protein output, vasodilatation, and VIP output.In morphological examinations, the inhibitory muscarinic M4 receptor occurred interacinarily in the gland.It is concluded that prejunctional muscarinic receptors, most likely of the M4 subtype, exert inhibitory modulation of the parasympathetic release of VIP in the ovine submandibular gland.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 405 30 Göteborg, Sweden.

ABSTRACT
In the in vivo experiments on anaesthetized sheep, it was presently examined whether muscarinic receptor antagonists with diverse selectivity affect the release of VIP in response to electrical stimulation of the parasympathetic chorda tympanic nerve differently, and if the changes in the release could be associated to altered secretory and vasodilator responses. The location of the muscarinic receptor subtypes was examined also. In the experiments, blood was collected out of the submandibular venous drainage before and during electrical stimulation of chorda tympani nerve in the absence and presence either of pirenzepine or methoctramine. While metchoctramine increased the output of protein, pirenzepine inhibited flow of saliva and increased protein output, vasodilatation, and VIP output. In morphological examinations, the inhibitory muscarinic M4 receptor occurred interacinarily in the gland. It is concluded that prejunctional muscarinic receptors, most likely of the M4 subtype, exert inhibitory modulation of the parasympathetic release of VIP in the ovine submandibular gland.

No MeSH data available.


Related in: MedlinePlus

Comparison of the changes in submandibular flow of saliva (A), submandibular protein output (B), submandibular vascular resistance (C), and VIP output (D) in response to chorda tympani stimulation at 8 Hz continuously for 10 minutes (from point of time 0 to 10; indicated by horizontal bar) in the absence  (▲) and in the presence (■) of methoctramine (left column of panels; 100 μg kg−1 IV) in 5 anesthetized sheep and in the absence (▲) and in the presence (■) of pirenzepine (right column of panels; 40 μg/kg iv) in 6 anesthetized sheep. Values are means ± S.E.M.
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fig1: Comparison of the changes in submandibular flow of saliva (A), submandibular protein output (B), submandibular vascular resistance (C), and VIP output (D) in response to chorda tympani stimulation at 8 Hz continuously for 10 minutes (from point of time 0 to 10; indicated by horizontal bar) in the absence (▲) and in the presence (■) of methoctramine (left column of panels; 100 μg kg−1 IV) in 5 anesthetized sheep and in the absence (▲) and in the presence (■) of pirenzepine (right column of panels; 40 μg/kg iv) in 6 anesthetized sheep. Values are means ± S.E.M.

Mentions: The intravenous administration of methoctramine 100 μg kg−1 (n = 5) had no effect neither on the flow of saliva (Figure 1(a)), the vascular resistance (Figure 1(c)), or on the submandibular output of VIP (Figure 1(d)). The overall output of protein increased in the presence of methoctramine (+110 ± 36%; P < .001), although no significance was attained for the separate points in time (Figure 1(b)). Pirenzepine (40 μg kg−1 IV; n = 6) significantly reduced the flow of saliva by about 30%. The overall vasodilator (+10 ± 5%; P < .01) as well as the protein secretory responses (+119 ± 30%; P < .001) both increased significantly. Both responses also attained a significant increase during the second half of the stimulation period.


Characterization of Prejunctional Muscarinic Receptors: Effects on the Release of VIP and Functional Responses and Receptor Expression in the Ovine Submandibular Gland.

Ryberg AT, Soukup O, Tobin G - Adv Pharmacol Sci (2009)

Comparison of the changes in submandibular flow of saliva (A), submandibular protein output (B), submandibular vascular resistance (C), and VIP output (D) in response to chorda tympani stimulation at 8 Hz continuously for 10 minutes (from point of time 0 to 10; indicated by horizontal bar) in the absence  (▲) and in the presence (■) of methoctramine (left column of panels; 100 μg kg−1 IV) in 5 anesthetized sheep and in the absence (▲) and in the presence (■) of pirenzepine (right column of panels; 40 μg/kg iv) in 6 anesthetized sheep. Values are means ± S.E.M.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2990107&req=5

fig1: Comparison of the changes in submandibular flow of saliva (A), submandibular protein output (B), submandibular vascular resistance (C), and VIP output (D) in response to chorda tympani stimulation at 8 Hz continuously for 10 minutes (from point of time 0 to 10; indicated by horizontal bar) in the absence (▲) and in the presence (■) of methoctramine (left column of panels; 100 μg kg−1 IV) in 5 anesthetized sheep and in the absence (▲) and in the presence (■) of pirenzepine (right column of panels; 40 μg/kg iv) in 6 anesthetized sheep. Values are means ± S.E.M.
Mentions: The intravenous administration of methoctramine 100 μg kg−1 (n = 5) had no effect neither on the flow of saliva (Figure 1(a)), the vascular resistance (Figure 1(c)), or on the submandibular output of VIP (Figure 1(d)). The overall output of protein increased in the presence of methoctramine (+110 ± 36%; P < .001), although no significance was attained for the separate points in time (Figure 1(b)). Pirenzepine (40 μg kg−1 IV; n = 6) significantly reduced the flow of saliva by about 30%. The overall vasodilator (+10 ± 5%; P < .01) as well as the protein secretory responses (+119 ± 30%; P < .001) both increased significantly. Both responses also attained a significant increase during the second half of the stimulation period.

Bottom Line: While metchoctramine increased the output of protein, pirenzepine inhibited flow of saliva and increased protein output, vasodilatation, and VIP output.In morphological examinations, the inhibitory muscarinic M4 receptor occurred interacinarily in the gland.It is concluded that prejunctional muscarinic receptors, most likely of the M4 subtype, exert inhibitory modulation of the parasympathetic release of VIP in the ovine submandibular gland.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 405 30 Göteborg, Sweden.

ABSTRACT
In the in vivo experiments on anaesthetized sheep, it was presently examined whether muscarinic receptor antagonists with diverse selectivity affect the release of VIP in response to electrical stimulation of the parasympathetic chorda tympanic nerve differently, and if the changes in the release could be associated to altered secretory and vasodilator responses. The location of the muscarinic receptor subtypes was examined also. In the experiments, blood was collected out of the submandibular venous drainage before and during electrical stimulation of chorda tympani nerve in the absence and presence either of pirenzepine or methoctramine. While metchoctramine increased the output of protein, pirenzepine inhibited flow of saliva and increased protein output, vasodilatation, and VIP output. In morphological examinations, the inhibitory muscarinic M4 receptor occurred interacinarily in the gland. It is concluded that prejunctional muscarinic receptors, most likely of the M4 subtype, exert inhibitory modulation of the parasympathetic release of VIP in the ovine submandibular gland.

No MeSH data available.


Related in: MedlinePlus