The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.

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Prolactin: Structure, Function, and Regulation of Secretion

The cardiovascular and other actions of angiotensin II (Ang II) are mediated by AT(1) and AT(2) receptors, which are seven transmembrane glycoproteins with 30% sequence similarity. Most species express a single autosomal AT(1) gene, but two related AT(1A) and AT(1B) receptor genes are expressed in rodents. AT(1) receptors are predominantly coupled to G(q/11), and signal through phospholipases A, C, D, inositol phosphates, calcium channels, and a variety of serine/threonine and tyrosine kinases. Many AT(1)-induced growth responses are mediated by transactivation of growth factor receptors. The receptor binding sites for agonist and nonpeptide antagonist ligands have been defined. The latter compounds are as effective as angiotensin converting enzyme inhibitors in cardiovascular diseases but are better tolerated. The AT(2) receptor is expressed at high density during fetal development. It is much less abundant in adult tissues and is up-regulated in pathological conditions. Its signaling pathways include serine and tyrosine phosphatases, phospholipase A(2), nitric oxide, and cyclic guanosine monophosphate. The AT(2) receptor counteracts several of the growth responses initiated by the AT(1) and growth factor receptors. The AT(4) receptor specifically binds Ang IV (Ang 3-8), and is located in brain and kidney. Its signaling mechanisms are unknown, but it influences local blood flow and is associated with cognitive processes and sensory and motor functions. Although AT(1) receptors mediate most of the known actions of Ang II, the AT(2) receptor contributes to the regulation of blood pressure and renal function. The development of specific nonpeptide receptor antagonists has led to major advances in the physiology, pharmacology, and therapy of the renin-angiotensin system.

https://pharmrev.aspetjournals.org/content/pharmrev/52/3/415.full.pdf

International Union of Pharmacology. XXIII. The Angiotensin II Receptors

Somatostatin and Its Receptor Family

Stress stimulates several adaptive hormonal responses. Prominent among these responses are the secretion of catecholamines from the adrenal medulla, corticosteroids from the adrenal cortex, and adrenocorticotropin from the anterior pituitary. A number of complex interactions are involved in the regulation of these hormones. Glucocorticoids regulate catecholamine biosynthesis in the adrenal medulla and catecholamines stimulate adrenocorticotropin release from the anterior pituitary. In addition, other hormones, including corticotropin-releasing factor, vasoactive intestinal peptide, and arginine vasopressin stimulate while the corticosteroids and somatostatin inhibit adrenocorticotropin secretion. Together these agents appear to determine the complex physiologic responses to a variety of stressors.

https://science.sciencemag.org/content/sci/224/4648/452.full.pdf

Stress hormones: Their interaction and regulation.

I. Introduction SOMATOSTATIN [somatotropin release-inhibiting factor (SRIF)] is a 14-amino acid polypeptide that is widely distributed throughout the central nervous system and peripheral tissues (Ref. 1; reviewed in Refs. 2–4). It potently inhibits basal and stimulated secretion from a wide variety of endocrine and exocrine cells and functions as a neurotransmitter/neuromodulator in the central nervous system with effects on locomotor activity and cognitive functions (1–12). Somatostatin also has antiproliferative effects and may be an important hormonal regulator of cell proliferation and differentiation (Refs. 13–15 and reviewed in Ref. 16). The first evidence for somatostatin-like activity came from studies of Krulich et al. (17), reported in 1968, who while looking for GHRF described a factor in hypothalamic extracts that inhibited GH secretion from anterior pituitaries in culture. Based on the identification of this inhibitory activity, Krulich et al. (17) proposed that the secretion of GH was regul...

https://www.cell.com/trends/neurosciences/pdf/0166-2236(93)90050-V.pdf

Molecular biology of somatostatin receptors

Opioid drugs, such as morphine, and the endogenous opioid peptides, namely the enkephalins, endorphins, and dynorphins, exert a wide spectrum of physiological and behavioral effects, including effects on pain perception, mood, motor control, and autonomic functions. These effects are mediated via membrane-bound receptors, of which the best characterized are the kappa, delta, and mu receptors. The existence of these distinct types of opioid receptors has recently been confirmed by molecular cloning. In the present study, we have examined the pharmacological profiles of the cloned kappa, delta, and mu receptors using a battery of widely employed opioid agents. Our results suggest that the cloned kappa and mu receptors have pharmacological characteristics similar to those of the endogenously expressed kappa 1 and mu receptors, respectively. The cloned delta receptor displays a pharmacological profile consistent with that of a delta 2 receptor. Opioid agents with abuse potential possess high affinities for the mu receptor. The availability of the cloned receptors will facilitate the identification and development of more specific and selective compounds with greater therapeutic potential and fewer undesirable side effects.

Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors.

Classification and nomenclature of somatostatin receptors.

Molecular biology of somatostatin receptors.

https://www.cell.com/trends/neurosciences/pdf/0166-2236(93)90194-Q.pdf

Terry Reisine

Papers

Molecular biology of somatostatin receptors

Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors.

Classification and nomenclature of somatostatin receptors.

Molecular biology of somatostatin receptors.

Molecular biology of opioid receptors