Ch3o

FIGURE 11-8 Structure of reserpine.

OCH3 ÖCH3

FIGURE 11-8 Structure of reserpine.

follows: increases in glycogenolysis and gluconeogene-sis in the liver, increased gluconeogenesis in skeletal muscle, increased inotropic effect (affecting the force of muscular contraction in the heart), increased amylase secretion by the salivary gland, relaxation of the uterine musculature, conversion of triglycerides to free fatty acids and glycerol in adipose, elevations in blood pressure, heart rate, and cardiac output (depending on amount of catecholamine), and dilation of bronchial musculature. Although norepinephrine is a pressor, its activity in this regard is much smaller than that of epinephrine. The structure of the /^-adrenergic receptor is shown in Figure 11-10.

B. Effects of Epinephrine on Glycogenolysis in the Liver

The breakdown of glycogen to glucose is accomplished by epinephrine operating at an «-adrenergic receptor on the hepatocyte membrane through a mechanism involving calcium ion fluxes. A scheme for the operation of the a-receptor in hepatocyte glycogenolysis is shown in Figure 11-11. As the result of a stressor

TABLE 11-2 Suggested Functions of Enkephalins" Function Explanatory remarks

Circulatory homeostatic mechanisms (chm) These peptides are released during intense stimulation and modify chm.

Primarily endorphins and enkephalins influence chm responses to stress at behavioral, endocrinological and neural levels.' Enhancement of cholecystokinin (CCK) release in brain CCK and enkephalins colocalized in several brain structures and they interact physiologically. The delta-opioid receptors may be involved in CCK release.'

Many opioid peptides are expressed within the olivocochlear efferent terminals involved in auditory function. Neurotransmitters of the olivocochlear efferents, such as enkephalins, dymorphins, acetylcholine may have antagonistic actions on auditory potentials. It is important to know whether adrenal chromaffin enkephalins can gain access to these nerves/

Heart failure is a stressor releasing opioids, endorphin, met-enkephalin, leu-enkephalin, dynorphin, casomorphin and others split out from precursor proteins. These play a role in improving hemodynamics but may be reduced in chronic heart failure through exhaustion of the opioid system reflected in reduced plasma levels of endorphin and lipotropin. Blood-brain barrier important here." Low doses of enkephalins potentiate immune responses Met-enk is more efficient when applied intracerebroventricularly but also active when given intrathecally. Met-enk is more potent than leu-enk. High doses of met-enk suppressed immune inflammatory reactions and skin reactions to protein antigen and other conditions/ Activation of endogenous enkephalinergic system by alcohol Alcohol induces the endogenous enkephalinergic system and subsequent intake involved in continuance of alcohol drinking occupation of delta opioid receptors which is involved in continued alcohol drinking/

Antagonistic actions on auditory potentials

Anti-stressing function in cases of heart failure

* An important consideration is whether adrenal medulla enkephalins can be transported to the sites of action listed in this Table or whether only locally produced enkephalins are involved. Blood-brain barrier function in the case of circulatory enkephalins has to be considered. b McCulbin, J. A. (1993). Stress and endogenous opioids: Behavioral and circulatory interactions. Biological Psychiat. 35, 91-122. c Ruiz-Gayo, M., Durieux, C., Fournie-Zaluski, M. C., and Roques, B. P. (1992). Stimulation of delta-opioid receptors reduces the in vivo binding of the cholecystokinin (CCK)-B selection agonist [3H]pBC 264: Evidence for a physiological regulation of CCKergic systems by endogenous enkephalins. J. Neurochem. 59, 1805-1811.

d Sakley, T. L., Kalish, R. B., Musiek, F. E., and Hoffman, D. W. (1991). Effects of opioid drugs on auditory evoked potentials suggest a role of lateral olivocochlear dymorphins in auditory function. Hearing Res. 55, 133-142. cLowe, H. (1991). Role of endogenous opioids in heart failure. Zeitschr. Knrdiol. 8, 47-51. ■^Jankovic, B. C. (1991). Enkephalins and immune inflammatory reactions. Acta Neurol. 13, 433-441.

% Froehlich, J. C., Zweifel, M., Harts, J., Lumeng, L., and Li, T. K. (1991). Importance of delta opioid receptors in maintaining high alcohol drinking. Psychopharmacology 103, 467-472.

hncho i J CH2

Unknown metabolites

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