Effects of Muscarinic Agonists and Depolarizing Agents on Inositol Monophosphate Accumulation in the Rabbit Vagus Nerve

Abstract

The effects of muscarinic agonists and depolarizing agents on inositol phospholipid hydrolysis in the rabbit vagus nerve were assessed by the measurement of [3H]inositol monophosphate production in nerves that had been preincubated with [3H]inositol. After 1 h of drug action, carbachol, oxotremorine, and arecoline increased the inositol monophosphate accumulation, though the maximal increase induced by these agonists differed. Addition of the muscarinic antagonists atropine or pirenzepine shifted the carbachol dose-response curves to the right, without decreasing the carbachol maximal stimulatory effects. The KB for pirenzepine was 35 nM, which is characteristic of muscarinic high-affinity binding sites coupled to phosphoinositide turnover and often associated with the M1 receptor subtype. On the other hand, agents known to depolarize or to increase the intracellular Ca2+ concentration, e.g., elevated extracellular K+, ouabain, Ca2+, and the Ca2+ ionophore A23187, also increased inositol monophosphate accumulation. These effects were not mediated by the release of acetylcholine, as suggested by the fact that they could not be potentiated by the addition of physostigmine nor inhibited by the addition of atropine. The Ca(2+)-channel antagonist Cd2+, also known to inhibit the Na+/Ca2+ exchanger, was able to block the effects of K+ and ouabain, but did not alter those of carbachol. These results suggest that depolarizing agents increase inositol monophosphate accumulation in part through elevation of the intracellular Ca2+ concentration and that muscarinic receptors coupled to phosphoinositide turnover are present along the trunk of the rabbit vagus nerve.

Axonal and glial currents activated during the post-tetanic hyperpolarization in non-myelinated nerve

“…The unmyelinated axons of the vagus nerve possess a large variety of voltage-gated channels, such as Na + channels, delayed rectifier K + channels, Ca 2+ -activated K + channels and Ca 2+ channels [12], as well as a number of receptors for neurotransmitters [29]. The present study demonstrates that they also display AR channels.…”

α, βI, βII, δ, and ε Protein Kinase C Isoforms and Compound Activity in the Sciatic Nerve of Normal and Diabetic Rats

“…This is compatible with the presence of a CaZ+-sensitive PLC isoform in RSN hydrolyzing preferentially PI over phosphatidylinositol bisphosphate (Natarajan and Schmid, 1987). Thus, CaZ+ influx, either under resting conditions (Sierro et al, 1992) or during electrical activity (Pralong and Straub, 1985) may be one of the elements linking phospholipid turnover (Goswami and Gould, 1985) and Na+,K+-ATPase function . This proposal is strengthened by our recent observation suggesting a tonic CaZ+-and staurosporine-sensitive aZP labeling of Na+,K+-ATPase a-subunit in normal RSN (Borghini et al, 1992).…”

“…resting peripheral nerve to be inhibited by inorganic Cat+ entry Mockers (Sierro et al, 1992). Therefore, CaZ+ influx may be an alternative pathway in the activation of PKC in peripheral nerve as demonstrated in other cell types (Biden et al, 1987;Ho et al, 1988).…”

In vivo phosphorylation of the Na,K-ATPase alpha subunit in sciatic nerves of control and diabetic rats: effects of protein kinase modulators.

“…In this way, Ca2+ would link the rapid basal turnover of specific inositol phospholipid pools, PKC, and Na,K-ATPase activity (11,35,36). Indeed, basal inositol monophosphate production is also inhibited by Ca2+-entry blockers in peripheral nerve (30). Furthermore, the rapid reduction of 32p labeling by staurosporine and, conversely, the pronounced increase in labeling by okadaic acid both indicate that a strong phosphatase activity permits a phosphorylation/dephosphorylation process with rapid turnover.…”