Motor activity and neurotransmitter release in the gastric fundus of streptozotocin-diabetic rats

https://doi.org/10.1016/0014-2999(91)90109-4Get rights and content

Abstract

As deficiencies of the cholinergic and non-adrenergic non-cholinergic innervation of the gastrointestinal tract have been described in diabetic rats, we studied the simultaneous release of, and muscular response to, acetylcholine, vasoactive intestinal polypeptide and adenosine-5′-triphosphate in isolated preparations of gastric fundus from control and 8-week streptozotocin-treated diabetic rats. Muscular responses were measured in longitudinal muscle strips prepared from one half of the gastric fundus and release was studied in the other half. The contractile response to acetylcholine and electrical field stimulation was not different in control and diabetic rats. In the presence of atropine, and when tone was increased with prostaglandin F, electrical field stimulation, vasoactive intestinal polypeptide and adenosine-5′-triphosphate induced relaxation with a similar response in control and diabetic rats. The basal release of acetylcholine, vasoactive intestinal polypeptide and adenosine-5′-triphosphate was not significantly different in control and diabetic rats. Electrical field stimulation significantly increased the release of the three substances and this increase was tetrodotoxin-sensitive. While the stimulation-induced increase of acetylcholine and vasoactive intestinal polypeptide was not different in control and in diabetic rats, the stimulation-induced release of adenosine-5′-triphosphate increased 3-fold in diabetic compared to control gastric fundus. Desensitization to α,β-methylene adenosine-5′-triphosphate reduced the relaxant response to adenosine-5′-triphosphate and to electrical field stimulation, suggesting a role of adenosine-5′-triphosphate in non-adrenergic non-cholinergic neurotransmission of rat gastric fundus. The reduction of the non-adrenergic non-cholinergic relaxation by α,β-methylene adenosine-5′-triphosphate was greater in diabetic tissues. This, with the increase in stimulation-induced adenosine-5′-triphosphate release, suggests that the purinergic component of the vagal non-adrenergic non-cholinergic response of the stomach may be increased in diabetics.

References (44)

  • T.V. Nowak et al.

    Evidence of abnormal cholinergic neuromuscular transmission in diabetic rat small intestine

    Gastroenterology

    (1986)
  • F.K. Okwuasaba et al.

    Relaxations of guinea-pig fundic strip by adenosine, adenine nucleotides and electrical stimulation: antagonism by theophylline and desensitization to adenosine and its derivatives

    European J. Pharmacol.

    (1977)
  • P.E. Stanley et al.

    Use of the liquid scintillation spectrometer for determining adenosine triphosphate by the luciferase enzyme

    Anal. Biochem.

    (1969)
  • N. Yildizoglu-Ari et al.

    Decreased gastro-intestinal responses to salbutamol and serotonin in streptozotocin-induced diabetes: improving effect of insulin in vivo and in vitro

    Gen. Pharmacol.

    (1988)
  • K. Aihara et al.

    Hyperreactivity of contractile response in gastric fundus smooth muscle from rats with diabetes induced by streptozotocin

    Arch. Int. Pharmacodyn.

    (1989)
  • V.M. Altan et al.

    Decreased gastro-intestinal responses to certain agonists in streptozotocin- and alloxan-diabetic rats in vitro

    Pharmacology

    (1987)
  • M. Ballman et al.

    Changes in the somatostatin, substance P and vasoactive intestinal polypeptide content of the gastrointestinal tract following streptozotocin-induced diabetes in the rat

    Diabetologia

    (1985)
  • K. Beck et al.

    Gastric motor responses elicited by vagal stimulation and purine compounds in the atropine-treated rabbit

    Br. J. Pharmacol.

    (1988)
  • E. Bülbring

    Measurements of oxygen consumption in smooth muscle

    J. Physiol.

    (1953)
  • G. Burnstock

    Nervous control of smooth muscle by transmitters, cotransmitters and modulators

    Experientia

    (1985)
  • G. Burnstock et al.

    Reversal of nerve damage in streptozotocin-diabetic rats by acute application of insulin in vitro

    Clin. Sci.

    (1988)
  • M. D'Amato et al.

    Comparison of the effect of vasoactive intestinal polypeptide and non-adrenergic non-cholinergic neurone stimulation in the cat gastric fundus

    European J. Pharmacol.

    (1988)
  • Cited by (50)

    • Effects of ghrelin on gastric distention sensitive neurons in the arcuate nucleus of hypothalamus and gastric motility in diabetic rats

      2013, Peptides
      Citation Excerpt :

      Our further fluo-immunohistochemistry staining and real-time PCR studies demonstrated that the expression of ghrelin receptor immunoreaction positive neurons and ghrelin receptor mRNA in the Arc were significantly lower in diabetic rats compared with the normal rats. Certainly, the decreased effects of ghrelin in the Arc on gastric motor index in DM rats perhaps also related with other evidence, such as visceral autonomic neuropathy [15,39], the loss of interstitial cells of Cajal (ICCs) [24], histological abnormalities for nerve fibers and varicosities in the intestinal myenteric plexus [7,27] and impaired neuromuscular transmission [10,32], impaired smooth muscle responsiveness to neurotransmitters [28], abnormal gastrointestional content and release of neurotransmitters [3,6] have all been reported. Furthermore, the neuronal effects of diabetes can vary with the neurotransmitter involved [4,6] or between different regions or nerve plexus of the gastrointestinal tract [2,5] in the STZ-induced diabetic rats.

    • Cellular distribution and functions of P2 receptor subtypes in different systems

      2004, International Review of Cytology
      Citation Excerpt :

      The functions claimed for the receptors together with key references are included. Release of purines following stimulation of NANC inhibitory nerves to the stomach and also from enteric nerves was first observed by Satchell and Burnstock (1971) and Su and colleagues (1971), respectively, and was confirmed in later studies (Belai et al., 1991). ATP was released from nerve varicosities isolated from the myenteric plexus of guinea pig ileum by 5-HT, ACh, and nicotine (Al-Humayyd and White, 1985; Hammond et al., 1988).

    View all citing articles on Scopus
    View full text