A study of the muscarinic receptor subtype mediating mucus secretion in the cat trachea in vitro

Gater, Paul R.; Alabaster, Valerie A.; Piper, I.

doi:10.1016/0952-0600(89)90029-x

Cited by 29 publications

(17 citation statements)

References 16 publications

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“…The pA2 value of 6.32 found for AF-DX 116 is within the range of 6.0-6.6 obtained for antagonism of smooth muscle contraction (Batink et al, 1987;Duckles et al, 1987;Lazareno & Roberts, 1988a;Moore et al, 1988;Roffel et al, 1988), whereas pA2 values obtained in the heart (6.9-7.5) (Batink et al, 1987;Duckles et al, 1987;Micheletti et al, 1987) are 4 to 16 times higher than the value we measured. Similarly, the pA2 value of 8.54 for 4-DAMP methobromide is close to the values found on various smooth muscle preparations (8.6-9.2) (Batink et al, 1987;Gater et al, 1987;Eglen et al, 1987;Moore et al, 1988;Roffel et al, 1988) but outside the range observed with cardiac preparations (7.7-8.2) (Batink et al, 1987;Gater et al, 1987;Lazareno & Roberts, 1988a). The conclusion that PI metabolism in bovine tracheal smooth muscle is brought about by M3 type muscarinic receptors concords with the M3 character of the muscarinic receptors that mediate contraction (see and references cited therein).…”

Section: Discussionsupporting

confidence: 84%

“…The finding that PI metabolism in bovine tracheal smooth muscle is mediated by M3-type muscarinic receptors is not completely unexpected. Firstly, muscarinic receptors in exocrine glands (which are typically of the M3 subtype, as assessed in binding (Lazareno & Roberts, 1988a) and secretion (Gater et al, 1987) studies) are also coupled to this second messenger system (Ek & Nahorski, 1988), although the receptor involved in PI turnover has not, as yet, been pharmacologically identified. Secondly, expression studies with different muscarinic receptor genes have shown that the putative M3 receptor subtype (HM4, mAChR III, m3) (Barnard, 1988) couples to PI turnover (but not to adenylate cyclase) in human kidney cells (Peralta et al, 1988) and NG108-15 neuroblastoma cells (Fukuda et al, 1988), whereas the M2 subtype is efficiently coupled to adenylate cyclase in human kidney cells (Peralta et al, 1988), chinese hamster ovary cells (Ashkenazi et al, 1987) and A9L fibroblasts (Jones et al, 1988), though it can, albeit poorly, also stimulate PI turnover in the first two of these cell types.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of the muscarinic receptor subtype involved in phosphoinositide metabolism in bovine tracheal smooth muscle

Roffel

Elzinga

Zaagsma

1990

British J Pharmacology

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1 The muscarinic receptor subtype involved in the methacholine-induced enhancement of phosphoinositide metabolism in bovine tracheal smooth muscle was identified by using the M2-selective antagonist AF-DX 116 and the M3-selective antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) methobromide, in addition to the M -selective antagonist pirenzepine, in a classical Schild analysis. 2 All the antagonists shifted the methacholine dose-response curve to the right in a parallel and concentration-dependent fashion, yielding Schild plots with slopes not significantly different from unity. The pA2 values (6.94, 6.32 and 8.54 for pirenzepine, AF-DX 116 and 4-DAMP methobromide respectively) indicate that it is the M3 (smooth muscle/glandular), but not the M2 (cardiac) muscarinic receptor subtype, present in this tissue, that mediates phosphoinositide turnover, in accordance with our previous contractile studies. 3 The results provide additional evidence for the involvement of phosphoinositide turnover in the pharmacomechanical coupling between muscarinic receptor stimulation and contraction in (bovine tracheal) smooth muscle.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Characterization of the muscarinic receptor subtype involved in phosphoinositide metabolism in bovine tracheal smooth muscle

Roffel

Elzinga

Zaagsma

1990

British J Pharmacology

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“…3A, B). The' steady-state I-V curve that was obtained while the sustained inward current was C -____present showed a reduction in the outward rectification in a potential range less negative than approximately -70 mV (tested up to -20 mV), where the M 500nA current 22,23 is activated (Fig. 3C).…”

Section: Tips -December 1989 Supp!eietmentioning

confidence: 93%

“…single species of ions, indicating the involvement of more than one ion species in the generation of the -' smooth current. Reversal potential measurements in _ 28S different media performed with EGTA-loaded oocytes 28S (see below) suggest that the smooth current evoked by 23 S . 23S activation of m2 or m4 is carried principally by Na+ and i8S .…”

Section: S-mentioning

confidence: 98%

Proceedings of the International Symposium on Subtypes of Muscarinic Receptors (4th), Held in Wiesbaden (Germany, F.R.) on 20-22 July 1989

Levine¹,

Birdsall²,

Hulme³

et al. 1990

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“…Using this approach, in pig trachea in vitro the muscarinic receptor subtype mediating S. I. Rawtnarinie atnd others mucus secretion wAas found to be of the A13 subtype (Yang, Farlev & Dwver, 1988), wrhereas in vitro in cat trachea the muscarinic secretory receptor may be of the 1\J subtype (Ishihara et at. 1992) or 'intermediate' betwTeen the All and Al subtypes (Gater, Alabaster & Piper, 1989). However, in the absence of cholinergic nerve stimulation, the enclogenous phlysiological contribution of the different muscarinic receptor subtypes, in particular the autoinhibitory vM2 receptor sub)type, is unclear from the studies cited.…”

mentioning

confidence: 99%

On muscarinic control of neurogenic mucus secretion in ferret trachea.

Ramnarine

Haddad

Khawaja

et al. 1996

The Journal of Physiology

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1 Muscarinic receptor subtypes mediating neurogenic mucus secretion in ferret trachea were characterized in vitro and in vivo using 35sQ, as a label for secreted mucus, and the muscarinic receptor antagonists telenzepine for the M1 receptor subtype, methoctramine for the M2 subtype and 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) for the M3 receptor. We also performed receptor binding and mapping studies. 2. Each muscarinic antagonist displaced [N-methyl-3H]scopolamine binding with high-affinity binding constant (KH) values of 1-9, 2-7 and 5 0 nm for telenzepine, methoctramine and 4-DAMP, respectively. Muscarinic M1 and M3 receptors localized to submucosal glands, whereas M2 receptors did not.3. In vitro, electrical stimulation (50 V, 10 Hz, 0 5 ms for 5 min) increased 35So4 output by 160%. Telenzepine did not inhibit the neurogenic secretory response at concentrations twoor twentyfold its KH value, nor did it inhibit secretion induced by acetylcholine (ACh). 4-DAMP inhibited neurogenic secretion by 80 and 95%, respectively, at concentrations twoand twentyfold its KH value, and also inhibited ACh-induced secretion. Methoctramine potentiated neurogenic secretion induced at 2-5 Hz (50 V, 0 5 ms for 5 min) in a dose-related (5-4-100 nM) manner with increases of 33-451 % above electrically stimulated values. Methoctramine did not potentiate secretion induced at 10 Hz and did not have any effect on ACh-induced secretion. 4. In vivo, vagal stimulation (10 V, 10 Hz, 2 ms for 8 min) increased output of 35S04 by -120%. Telenzepine had no significant effect on neurogenic secretion. Methoctramine approximately doubled the stimulated response, whereas 4-DAMP abolished the stimulated secretory response. 5. We conclude that in ferret trachea, cholinergic nerve stimulation increases mucus secretion via muscarinic M3 receptors on the submucosal glands. The magnitude of the secretory response is regulated by neuronal M2 muscarinic receptors. The muscarinic M1 receptors localized to the submucosal glands do not appear to be involved with mucus secretion.Cholinergic nerves are the dominant neural pathway involved in control of a number of airway functions, including mucus secretion (Rogers, 1996). Physiological responses to cholinergic nerve stimulation are mediated via cholinergic muscarinic receptors (Barnes, 1993). Four subtypes of muscarinic receptor (M1-M3, and possibly M4) can be demonstrated pharmacologically, although the muscarinic antagonist drugs currently available are not highly selective for the different receptor subtypes (Eglen, Reddy & Watson, 1994). In the airways, Ml receptors are localized to parasympathetic ganglia, submucosal glands and, in humans, to the alveolar walls (Barnes, 1993

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A study of the muscarinic receptor subtype mediating mucus secretion in the cat trachea in vitro

Cited by 29 publications

References 16 publications

Characterization of the muscarinic receptor subtype involved in phosphoinositide metabolism in bovine tracheal smooth muscle

Characterization of the muscarinic receptor subtype involved in phosphoinositide metabolism in bovine tracheal smooth muscle

Proceedings of the International Symposium on Subtypes of Muscarinic Receptors (4th), Held in Wiesbaden (Germany, F.R.) on 20-22 July 1989

On muscarinic control of neurogenic mucus secretion in ferret trachea.

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