Abstract:
:Studies demonstrate that some colon cancers possess receptors for various gastrointestinal hormones or neurotransmitters, the occupation of which can affect growth. These results are limited because frequently only a small number of tumors are studied, only 1 or 2 receptors are sought, and the effect on cell function is not investigated. In the present study, 10 recently characterized human colon cancer cell lines were studied to determine whether they possess receptors for any of 12 different gastrointestinal hormones or neurotransmitters and to determine whether these receptors mediate changes in cellular function. Each of the cell lines exhibited receptors for at least one radioligand. Receptors for vasoactive intestinal peptide (VIP) and muscarinic cholinergic agents occurred on 60%, bombesin and gastrin on 30%, beta-adrenergic agents and gastrin-releasing peptide (GRP) on 20%, and somatostatin, opiates, neuromedin B, and substance P on 10%. Analysis of [3H]N-methylscopolamine binding revealed a Kd of 0.2 nM for N-methylscopolamine with a binding capacity of 2500 sites/cell. With the agonist carbamylcholine, the receptor exhibited 2 classes of binding sites: one of high affinity (Kd 55 microM) representing 75% of the binding sites and one of low affinity (Kd 0.3 mM) representing 25% of the binding sites. Analysis of 125I-[Tyr4]bombesin binding revealed a receptor of high affinity (Kd 2.1 microM) with a binding capacity of 3300 sites/cell. Inhibition of binding by agonists revealed relative potencies of 125I-[Tyr4]bombesin greater than GRP much greater than neuromedin B, and two recently described antagonists were similar in potency to GRP. Analysis of 125I-VIP binding revealed a receptor having 2 classes of binding sites: one of high affinity (Kd 3.6 nM) and one of low affinity (Kd 1.7 microM) which represented the majority of the 5.5 x 10(6) binding sites/cell. The relative potencies of agonists were VIP greater than helodermin greater than peptide histidine methionine greater than secretin. Evaluation of biological activity mediated by the muscarinic cholinergic and bombesin receptors revealed an increase of intracellular calcium and of inositol triphosphate by specific receptor agonists. The presence or absence of receptors detected by binding correlated closely with the ability of selective receptor agonists to alter cell function. These results demonstrate the presence of several different receptors for gastrointestinal hormones or neurotransmitters, some described for the first time, on human colon cancer cell lines, including bombesin-related peptides, VIP, somatostatin, substance P, beta-adrenergic agents, calcitonin gene-related peptide, gastrin, muscarinic cholinergic agents, and opiates.(ABSTRACT TRUNCATED AT 400 WORDS)
journal_name
Cancer Resjournal_title
Cancer researchauthors
Frucht H,Gazdar AF,Park JA,Oie H,Jensen RTsubject
Has Abstractpub_date
1992-03-01 00:00:00pages
1114-22issue
5eissn
0008-5472issn
1538-7445journal_volume
52pub_type
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