Simulatory effect of porcine insulin on noradrenaline secretion in guinea‐pig ileum myenteric nerve terminals

Abstract

1 The eect of insulin on the release of noradrenaline (NA) from nerve terminals was investigated in isolated ileal synaptosomes of guinea-pig. Release was determined as the amount of NA, quanti®ed by h.p.l.c.-electrochemical detection, from samples incubated with insulin minus that in parallel blanks treated with some volume of vehicle. 2 Porcine insulin stimulated the secretion of NA in a concentration-dependent manner from 0.01 i.u. ml 71 , while the value of lactate dehydrogenase in the incubated medium was not in¯uenced by insulin. 3 The presence of insulin receptors in this preparation was illustrated by immunoblotting with insulin receptor monoclonal antibodies. 4 The release of NA by insulin was reduced by guanethidine and bretylium and it was markedly lowered in the samples obtained from guinea-pigs that had received an intraperitoneal injection of DSP-4, the noradrenergic neurotoxin. 5 Tetrodotoxin attenuated the action of insulin at concentrations sucient to block sodium channels. The depolarizing eect of insulin on the membrane potential was also illustrated by a concentrationdependent increase in the¯uorescence of bisoxonol, a potential-sensitive dye. 6 The action of insulin was attenuated by removal of calcium chloride from the bathing medium. The induction of calcium ion in¯ux by insulin into the synaptosomes is supported by the inhibitory eects of the calcium channel blockers o-conotoxin GVIA (for the N-type channels) and nifedipine (for the L-type channels). 7 These ®ndings suggest that insulin can stimulate NA release from noradrenergic terminals via activation of calcium in¯ux.

Insulin Regulates Neuronal M2Muscarinic Receptor Function in the Ileum of Diabetic Rats

“…Insulin has been demonstrated to increase noradrenaline release from sympathetic nerves in the guinea pig ileum (Cheng et al, 1997). This increase may be due in part to inhibition of neuronal M 2 muscarinic receptors.…”

Histamine H3 receptors mediate inhibition of noradrenaline release from intestinal sympathetic nerves

“…Moreover, there is both clinical and experimental evidence that sympathetic dysfunctions are implicated in the pathophysiology of several digestive orders (McIntyre & Thompson, 1992). Previous studies have shown that noradrenergic nerve terminals supplying the digestive tract are equipped with presynaptic heteroreceptors, including muscarinic, opioid and insulin receptors (Fuder & Muscholl, 1995; Cheng et al ., 1997), the activation of which results in positive or negative changes of noradrenaline release. However, the possibility that prejunctional histamine receptors participate in the control of intestinal sympathetic neurotransmission has not yet been examined.…”