Characterization of functional melanotropin receptors in lacrimal glands of the rat

doi:10.1016/0196-9781(90)90046-8

Peptides

Volume 11, Issue 3, May–June 1990, Pages 477-483

https://doi.org/10.1016/0196-9781(90)90046-8 Get rights and content

Abstract

The specific melanotropin (MSH) binding sites of rat lacrimal glands were characterized with respect to anatomic distribution, peptide specificity and selectivity, and coupling to a biological response. Tissue distribution of MSH binding sites was determined by autoradiography following in situ binding of a radiolabeled, biologically active preparation of a superpotent α-MSH analog, [¹²⁵I]-[Nle⁴,D-Phe⁷]-α-MSH ([¹²⁵I]-NDP-MSH). Intense, specific (i.e., α-MSH-displaceable) [¹²⁵I]-NDP-MSH binding was observed throughout lacrimal acinar tissue, but not in ducts or stroma. In freshly isolated lacrimal acinar cells, specific binding of [¹²⁵I]-NDP-MSH was maximal within 30 min and rapidly reversible, with a dissociation half-time of about 15 min. A number of melanotropins {;α-MSH, [N,O-diacetyl-Ser¹]-α-MSH, [des-acetyl-Ser¹]-α-MSH, β-MSH, ACTH(1–24) and ACTH(1–39)}; were recognized by these binding sites, as assessed by their inhibition of [¹²⁵I]-NDP-MSH binding; NDP-MSH was the most potent ( $IC_{50} =1.3×10^{−9} M$ ). In contrast, other peptides, including ACTH(4–10) and the nonmelanotropic peptides VIP, substance P, somatostatin, and ACTH(18–39) (CLIP), had no effects on tracer binding. In isolated lacrimal acinar cells, α-MSH and NDP-MSH stimulated intracellular cyclic AMP accumulation. We conclude that lacrimal acinar cells express functional receptors recognizing melanotropins, suggesting that the lacrimal gland may be a target for physiological regulation by endogenous melanotropins.

References (20)

M.M. Cripps et al.
Adrenocorticotropic hormone stimulation of lacrimal peroxidase secretion
Exp. Eye Res.
(1987)
T.L. O'Donohue et al.
Identification, characterization and stereotaxic mapping of intraneuronal α-melanocyte stimulating hormone-like immunoreactive peptides in discrete regions of the rat brain
Brain Res.
(1979)
Z. Abdel-Malek et al.
Prolonged stimulation of S91 melanoma tyrosinase by substituted α-melanotropins
Cancer Res.
(1985)
D.A. Dartt
Signal transduction and control of lacrimal gland protein secretion: A review
Curr. Eye Res.
(1989)
D.A. Dartt et al.
Vasoactive intestinal polypeptide stimulation of protein secretion from rat lacrimal gland acini
Am. J. Physiol.
(1984)
L.E. Hann et al.
Morphology and function of lacrimal gland acinar cells in primary culture
Invest. Ophthalmol. Vis. Sci.
(1989)
M. Herkenham et al.
Light microscopic localization of brain opiate receptors: A general autoradiographic method which preserves tissue quality
J. Neurosci.
(1982)
R.H. Jahn et al.
Adrenocorticotropic hormone and α-melanocyte stimulating hormone induce secretion and protein phosphorylation in the rat lacrimal gland by activation of a cAMP-dependent pathway
Eur. J. Biochem.
(1982)
K. Kameyama et al.
Interferons modulate the expression of hormone receptors on the surface of murine melanoma cells
J. Clin. Invest.
(1989)
H.G. Klemcke
Characterization of porcine adrenocorticortical adrenocorticotropic hormone (ACTH) receptors

There are more references available in the full text version of this article.

Cited by (22)

Tear film and ocular surface neuropeptides: Characteristics, synthesis, signaling and implications for ocular surface and systemic diseases
2022, Experimental Eye Research
Citation Excerpt :
Melanocortin receptors (members of the rhodopsin family of 7-transmembrane domain G protein-coupled receptors) are expressed in the acinar cells of the lacrimal glands and the rest of the ocular surface (Entwistle et al., 1990). Alpha-MSH binds melanocortin receptors (Entwistle et al., 1990; Shiratori et al., 2004) and has been shown to enhance protein secretion in vitro from the lacrimal gland cells (Entwistle et al., 1990). In conjunction with VIP it can have an anti-lymphangiogenic role in the cornea (Bock et al., 2016) Alpha-MSH controls inflammation via downregulation of dectin-1, decreases fungal load and promotes tissue repair in a mouse model of Aspergillus fumigatus keratitis (Li et al., 2021).
Ocular surface neuropeptides are vital molecules primarily involved in maintaining ocular surface integrity and homeostasis. They also serve as communication channels between the nervous system and the immune system, maintaining the homeostasis of the ocular surface. Tear film and ocular surface neuropeptides have a role in disease often due to abnormalities in their synthesis (either high or low production), signaling through defective receptors, or both. This creates imbalances in otherwise normal physiological processes. They have been observed to be altered in many ocular surface and systemic diseases including dry eye disease, ocular allergy, keratoconus, LASIK-induced dry eye, pterygium, neurotrophic keratitis, corneal graft rejection, microbial keratitis, headaches and diabetes. This review examines the characteristics of neuropeptides, their synthesis and their signaling through G-protein coupled receptors. The review also explores the types of neuropeptides within the tears and ocular surface, and how they change in ocular and systemic diseases.
TFOS DEWS II Sex, Gender, and Hormones Report
2017, Ocular Surface
Citation Excerpt :
Thus, the influence of interrupting the hypothalamic-pituitary axis on androgen target organs appears to be site-specific. Anterior pituitary hormones, either directly or indirectly (e.g. through control of steroid, thyroxine and insulin), modulate the growth, differentiation and secretion of the lacrimal gland [360,410,411,514,616,737–740,742,748–750], as well as meibomian gland function [751]. The effects of growth hormone are described in Section 3.5.
One of the most compelling features of dry eye disease (DED) is that it occurs more frequently in women than men. In fact, the female sex is a significant risk factor for the development of DED. This sex-related difference in DED prevalence is attributed in large part to the effects of sex steroids (e.g. androgens, estrogens), hypothalamic-pituitary hormones, glucocorticoids, insulin, insulin-like growth factor 1 and thyroid hormones, as well as to the sex chromosome complement, sex-specific autosomal factors and epigenetics (e.g. microRNAs).
In addition to sex, gender also appears to be a risk factor for DED. “Gender” and “sex” are words that are often used interchangeably, but they have distinct meanings. “Gender” refers to a person’s self-representation as a man or woman, whereas “sex” distinguishes males and females based on their biological characteristics. Both gender and sex affect DED risk, presentation of the disease, immune responses, pain, care-seeking behaviors, service utilization, and myriad other facets of eye health.
Overall, sex, gender and hormones play a major role in the regulation of ocular surface and adnexal tissues, and in the difference in DED prevalence between women and men. The purpose of this Subcommittee report is to review and critique the nature of this role, as well as to recommend areas for future research to advance our understanding of the interrelationships between sex, gender, hormones and DED.
The Role of the Melanocortin System in Drug and Alcohol Abuse
2017, International Review of Neurobiology
The melanocortin (MC) system is composed of different peptides centrally produced by proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus (N.Arc) and the medulla. These peptides act through five subtypes of melanocortin receptors (MCRs) that belong to the family of seven-transmembrane G-protein-coupled receptors that are coupled through Gα_s signaling pathways. MC3R and MC4R are the predominant MCR subtypes in the brain, and they are widely expressed in brain regions thought to modulate drug self-administration, including the nucleus accumbens, the hypothalamus, and the ventral tegmental area. The MC system is unique in terms of having an endogenous antagonist/inverse agonist, agouti-related protein (AgRP), also produces in the N.Arc and secreted in terminals expressing MCRs. There is a large body of research showing the role of the MC and AgRP systems in neurobiological responses to drugs of abuse, in particular, neurobiological responses to ethanol. In this chapter, we discuss the most recent evidence that supports the role of the MC/AgRP systems in modulating neurobiological responses to drugs of abuse, with a focus on ethanol consumption.
Calcium signaling in lacrimal glands
2014, Cell Calcium
Lacrimal glands provide the important function of lubricating and protecting the ocular surface. Failure of proper lacrimal gland function results in a number of debilitating dry eye diseases. Lacrimal glands secrete lipids, mucins, proteins, salts and water and these secretions are at least partially regulated by neurotransmitter-mediated cell signaling. The predominant signaling mechanism for lacrimal secretion involves activation of phospholipase C, generation of the Ca²⁺-mobilizing messenger, IP₃, and release of Ca²⁺ stored in the endoplasmic reticulum. The loss of Ca²⁺ from the endoplasmic reticulum then triggers a process known as store-operated Ca²⁺ entry, involving a Ca²⁺ sensor in the endoplasmic reticulum, STIM1, which activates plasma membrane store-operated channels comprised of Orai subunits. Recent studies with deletions of the channel subunit, Orai1, confirm the important role of SOCE in both fluid and protein secretion in lacrimal glands, both in vivo and in vitro.
Melanocortin receptors and their accessory proteins
2011, Molecular and Cellular Endocrinology
Citation Excerpt :
The MC5R is ubiquitously expressed in several tissues, including skin, adrenal gland, adipose tissue, kidney, lymph nodes, liver, skeletal muscle and exocrine glands (Barrett et al., 1994; Chen et al., 1997; Chhajlani et al., 1993; Gantz et al., 1994; Griffon et al., 1994; Labbe et al., 1994). It is implicated in the production of sebaceous lipids (Chen et al., 1997), protein and tear secretion by the lacrimal gland (Entwistle et al., 1990) and also has a role in immune regulation (Taylor and Namba, 2001). See Table 1 for the biological distribution and functions of the melanocortin receptor family.
The melanocortin receptor family consists of 5 members which belong to the GPCR superfamily. Their specific ligands, the melanocortins are peptide hormones which are formed by the proteolytic cleavage of the proopiomelanocortin (POMC) protein. It is now recognised that certain GPCRs require accessory proteins for their function. Like these GPCRs the melanocortin receptor family is also known to be associated with accessory proteins that regulate their function.
In this review we will summarise the accessory proteins involved in the function of the 5 melanocortin receptors and in particular focus on the melanocortin 2 receptor accessory protein (MRAP) which is crucial for the function of the MC2R.
Androgen regulation of gene expression in the mouse lacrimal gland
2005, Journal of Steroid Biochemistry and Molecular Biology
The objective of this study was to determine the nature and extent of androgen influence on gene expression in the lacrimal gland. Lacrimal glands were obtained from orchiectomized mice that had been treated with testosterone or vehicle for 2 weeks, as well as from testicular feminized mice and their Tabby controls. Samples were pooled according to experiment, processed for the isolation of RNA, and analyzed for differentially expressed mRNAs by using primarily CodeLink Bioarrays, GEM 1 and 2 gene chips and quantitative real-time PCR (qPCR) procedures. Gene chip data were analyzed with GeneSifter.Net software. Our results demonstrate that testosterone regulates the expression of over 2000 genes in the lacrimal gland. Gene ontologies most affected by androgen treatment included those related to cell growth, proliferation and metabolism, cell communication and transport, nucleic acid binding, signal transduction and receptor activities. Our findings also indicate that androgen action may be mediated, at least in part, through classical androgen receptors, and may contribute to the sex-related differences in gene expression of lacrimal tissue. Overall, these results support our working hypothesis that androgen action on the lacrimal gland is mediated primarily through a receptor-associated regulation of gene transcription.

View all citing articles on Scopus

View full text

ArticleCharacterization of functional melanotropin receptors in lacrimal glands of the rat

Abstract

Exp. Eye Res.

Brain Res.

Prolonged stimulation of S91 melanoma tyrosinase by substituted α-melanotropins

Cancer Res.

Signal transduction and control of lacrimal gland protein secretion: A review

Curr. Eye Res.

Vasoactive intestinal polypeptide stimulation of protein secretion from rat lacrimal gland acini

Am. J. Physiol.

Morphology and function of lacrimal gland acinar cells in primary culture

Invest. Ophthalmol. Vis. Sci.

Light microscopic localization of brain opiate receptors: A general autoradiographic method which preserves tissue quality

J. Neurosci.

Adrenocorticotropic hormone and α-melanocyte stimulating hormone induce secretion and protein phosphorylation in the rat lacrimal gland by activation of a cAMP-dependent pathway

Eur. J. Biochem.

Interferons modulate the expression of hormone receptors on the surface of murine melanoma cells

J. Clin. Invest.

Characterization of porcine adrenocorticortical adrenocorticotropic hormone (ACTH) receptors

Article
Characterization of functional melanotropin receptors in lacrimal glands of the rat