Nonshivering thermogenesis in the rat. I. The relation between drug-induced changes in thermogenesis and changes in the concentration of plasma cyclic AMP

Abstract

Barbital-sedated, cold-acclimated (CA) or warm-acclimated (WA) rats were given different doses and combinations of noradrenaline, theophylline, and the adrenergic-blocking agents propranolol and phentolamine, to stimulate or inhibit calorigenesis in various ways. To see whether the effects of these drugs on calorigenesis could be ascribed to effects on the adenylate cyclase (EC 4.6.1.1) - cyclic AMP system, and to try to assess thereby the significance of this system in the regulation of nonshivering thermogenesis (NST), changes in the concentration of plasma cyclic AMP were measured as an index (Broadus, A.E., Hardman, J.G., Kaminsky, N. I., Ball, J. H., Sutherland, E.W., and Liddle, G. W.: 1971. Ann. N.Y. Acad. Sci. 185, 50-60) of changes in tissue levels of cyclic AMP. In CA rats, which have a severalfold greater capacity for NST than WA rats, calorigenic responses to noradrenaline, theophylline, noradrenaline plus theophylline, or phentolamine plus theophylline were as much as four times larger than in WA rats, However, the changes in level of plasma cyclic AMP produced by each of these and other treatments were virtually the same for both groups. It would appear, therefore, that the difference between WA and CA rats in ability to produce heat by NST is not a function of the amplitude of changes in tissue levels of cyclic AMP. Nevertheless, it was also observed, and was particularly striking in CA rats, that when a drug or combination of drugs had a stimulatory, inhibitory, or synergistic effect on calorigenesis, it had a similar effect with respect to elevation of plasma cyclic AMP. Altogether, the results indicate that adenylate cyclase and cyclic AMP are likely to be participants in the regulation of NST in the rat, but that they would be subservient in this regard to whatever factors are responsible for acclimation-related differences in capacity for NST.

The effect of glucagon and prostaglandin E1 on cyclic AMP levels in liver of heat exposed hamsters

“…These findings are partly supported by the data described by Foster et al (1977), indicating higher plasma cyclic AMP levels in warm acclimated rats as compared to cold accli¬ mated rats. It was suggested that the changes in cyclic AMP levels are related to the changes in the rate of liver degradation and liver regeneration occurring during the period of heat exposure (Chayoth et al 1977).…”

Effect of aminophylline on metabolic and thermoregulatory responses during hypothermia associated with cold exposure in lambs

“…One of the means by which catecholamines enhance metabolism is through stimulation of adenylate cyclase resulting in formation of 3′, 5′ adenosine monophosphate in target tissues (Lundholm et al 1968;Robison et al 1971). Indeed, Foster et al (1977) demonstrated a close parallelism between changes in plasma cAMP and calorigenic responses to norepinephrine in cold acclimated rats.…”