On the association between transmitter secretion and the release of adenine nucleotides from mammalian motor nerve terminals.

Abstract

SUMMARY1. Conventional electrophysiological techniques were used to record from isolated rat phrenic nerve-hemidiaphragm preparations. After periods of rest (20 min) or nerve stimulation (7/sec for 20 min) the bathing medium of the preparation was removed and assayed for adenosine triphosphate (ATP) and adenosine diphosphate (ADP) using a sensitive modification of the firefly luciferase method (Silinsky, 1974 6. These results in conjunction with experiments on the hydrolysis of exogenous ATP suggest that ATP is released from the motor nerve ending and is subsequently degraded by enzymatic activity. It is also suggested that the released nucleotide may be derived from the cholinergic vesicle.

Purinergic signalling in the musculoskeletal system

“…Recently, osteoclasts derived from mouse bone marrow were shown to express all P2 receptors, with the exception of the P2X6 and P2Y 4 receptors [119]. This study also demonstrated large differences in the expression levels of the different P2 receptors, with the P2Y 6 receptor being the most abundant [119].…”

“…Recently, activation of the P2Y 6 receptor by UDP has been shown to stimulate osteoclast formation and activity [119]. Consistent with a role for this receptor in bone resorption, osteoclasts derived from P2Y 6 receptor knockout mice displayed defective function [119]. Analysis of P2Y 6 receptor knockout mice by μCT revealed increased cortical bone in the long bones and spine [119].…”

“…P2Y 1 , P2Y 2 and P2Y 4 receptors were shown to be only temporarily expressed in embryos and were down-regulated in postnatal life. Differentiating skeletal muscle C2C12 cells express P2Y 1 , P2Y 2 , P2Y 4 and P2Y 6 receptor mRNA [70]. At the transcriptional level, P2Y 1 and P2Y 2 receptors have been identified in human skeletal muscle [76,77] and ATP stimulates an increase in [Ca 2+ ] i in human myotubes [78].…”

“…Initial studies using rat long bonederived osteoclasts showed expression of mRNA and protein for the P2X2, P2X4, P2X7, P2Y 1 and P2Y 2 receptors [166]. Human osteoclasts generated from peripheral blood were later shown to express the P2X1, P2X4, P2X7, P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 and P2Y 11 receptors [258]. Recently, osteoclasts derived from mouse bone marrow were shown to express all P2 receptors, with the exception of the P2X6 and P2Y 4 receptors [119].…”

“…They also reported that the sensitivity of the preparation to acetylcholine (ACh) was greatly increased by previous application of ATP [2]. ATP was later shown to be released together with ACh from cholinergic nerves in various tissues, including the electric organ of elasmobranch fish [3,4] and phrenic nerve endings in the rat diaphragm [5,6]. However, it was not recognised at the time as a cotransmitter, but was considered as a molecule involved in the vesicular uptake and storage of the neurotransmitter ACh.…”