The Effect of Ethanol on Inhibitory and Motor Responses in the Rat and Rabbit Anococcygeus and the Bovine Retractor Penis Muscles

Abstract

Ethanol (200 mm) reduced the response to inhibitory nerve stimulation in the rat and rabbit anococcygeus and the bovine retractor penis (BRP) muscles. Ethanol also reduced the response to the inhibitory extract from the BRP consistent with the inhibitory factor in these extracts playing some part in the response to inhibitory nerve stimulation. Ethanol's effect on the response to other inhibitory stimuli was examined in the rabbit anococcygeus and the BRP. In the anococcygeus the response to carbachol was reduced, to bradykinin and isobutylmethylxanthine (IBMX) unaltered, and to isoprenaline and adenosine 5′‐triphosphate (ATP) potentiated. In the BRP responses to IBMX and sodium nitroprusside were unaltered but in this tissue the response to isoprenaline was reduced. Ethanol's ability to reduce inhibitory responses is, therefore, selective and confined to inhibitory nerve stimulation, inhibitory extract, carbachol and, in the BRP, isoprenaline. Ethanol reduced the rate of development of inhibition even where the magnitude of the inhibitory response was unaltered. In the rat anococcygeus, ethanol (200 mm) potentiated the response to motor nerve stimulation and to noradrenaline (NA) at low frequencies and low concentrations respectively. Higher ethanol concentrations (400 mm) reduced the response to both motor nerve stimulation and NA. The motor response to carbachol was also reduced. Ethanol (200 mm) itself caused an easily reversible contraction in all three tissues. This was not due to the release of NA but was highly sensitive to the removal of external calcium from the medium. A unified explanation of these varied effects of ethanol based on a reduction in membrane binding of calcium and a reduced efficiency of receptor coupling is suggested.

Effects of ethanol and other aliphatic alcohols on NO‐mediated relaxations in rat anococcygeus muscles and gastric fundus strips

“…Both these effects are produced by other agents that inhibit nitrergic nerve-stimulation-induced relaxations, such as NO synthase inhibitors, haemoglobin and methylene blue (Rand, 1992a), and are attributable to removal of a NO-mediated relaxant influence. However, ethanol also reduced the contractile action of noradrenaline (Gillespie et al, 1982).…”

“…In addition, effects other than interaction with NO may also be involved in the actions produced by alcohols, especially at the relatively high concentrations used, since the tone of the muscle was decreased by all the alcohols except ethanol. It is possible that this reduction in tone is due to disordering of the cell membrane by the alcohols, causing a reduction of the intracellular calcium concentration in the smooth muscle cells, as suggested by Gillespie et al (1982).…”

“…The findings could be explained either by inhibition of the guanylate cyclase/cyclic GMP mechanism mediating the relaxation of the smooth muscle, or by an interaction of ethanol with the released NANC transmitter, NO or a NO-related compound, resulting in its inactivation. However, SNP-induced relaxations of the bovine retractor penis muscle were not affected by ethanol (Gillespie et al, 1982), although it reduced the response to the inhibitory factor (IF) isolated from the bovine retractor penis muscle (Gillespie et al, 1982), which has recently been identified as a NO-donating nitrosothiol (Kerr et al, 1992).…”

An inhibitory effect of ethanol on adrenergic neuromuscular transmission in the guinea-pig vas deferens.

“…The temperature was maintained at 35±1 °C, and the pH was adjusted to 7.2-7. 4. Drugs were applied to the tissue by changing the inflow to the organ bath from normal Krebs solution to Krebs containing the appropriate drug, without alteration of flow rate.…”

“…It has been reported that ethanol increases the spontaneous noradrenaline release from the rat vas deferens (1), but it decreases the stimulated release of noradrenaline from the rabbit cardiac sympathetic nerves (2,3). Recently, Gillespie et al (4) have shown that ethanol reduces the motor response to adrenergic nerve stimulation in the rat anococcygeus muscle. Despite these apparent effects on the adrenergic systems, there have been little electrophysiological data on the direct cellular effects of ethanol.…”