GPCR expression in tissues and cells: are the optimal receptors being used as drug targets?

G-protein-coupled receptors [GPCRs, also known as 7-transmembrane (7-TM) receptors] comprise the largest family of membrane receptors in humans and other species and, in addition, represent the greatest number of current drug targets. In this article, we review methods to define GPCR expression and data indicating that individual cells express >100 different GPCRs. Results from studies that have quantified expression of these receptors lead us to conclude that the optimal GPCRs may not be currently used as therapeutic targets. We propose that studies of GPCR expression in individual cells will likely reveal new insights regarding cellular physiology and therapeutic approaches. Findings that define and characterize the most highly expressed GPCRs thus have important potential in terms of identifying new drug targets and novel therapies directed at a wide range of clinical disorders.

Mammary growth patterns in guinea pigs during puberty, pregnancy and lactation.

Mammary gland growth patterns were studied in 110 guinea pigs during the growth phase, pregnancy and lactation. Body weight changes were studied and, in addition, mammary indices were wet weight, dry fat-free tissue (DFFT), deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Statistical analyses were mathematical regression models to best fit the actual data. These included linear, quadratic, cubic, and several forms of exponential regression models. Data were separated into growth phase (60 guinea pigs in 10 age groups), pregnancy (20 guinea pigs in 4 groups), and lactation (30 guinea pigs in 6 groups). Data during pregnancy and the first 5 days of lactation were pooled and analyzed also because mammary growth continued beyond pregnancy to Day 5 of lactation. Mammary wet weight increased according to a cubic expression in the growth phase, while mammary DFFT, DNA and RNA were rectilinear through 200 days of age. During pregnancy and the first 5 days of lactation, mammary growth parameters followed the pattern of an exponential equation. Daily rates of increase for mammary DFFT and DNA were twice the rate for mammary wet weight. During lactation, mammary gland indices increased to Day 5 and then decreased gradually from Day 10 to Day 20. The best mathematical models for these change were those which are used to describe lactation curves, but all mammary gland indices decreased later and more gradually than milk production. Comparisons in growth rates of guinea pig mammary glands were made with those published for dairy goats and dairy cows. Rates of mammary DNA changed inversely to lengths of gestation in these 3 species.

Mammary growth pattern in goats during pregnancy and lactation.

Nine groups of five dairy goats from four breeds, with each breed represented at least once in each group, were in our experiment to measure mammary gland growth. Groups were virgins, days 90 to 100 pregnancy, 5 days prepartum (145 days pregnancy), 1 or 2 days prepartum, and 1 or 2, 5, 10, 15, and 30 days in lactation. Virgins were 19 mo old while all others had one pregnancy and lactation prior to experiment. Indices of mammary growth included untrimmed and trimmed wet weights of udders, dried fat-free tissue weights, deoxyribonucleic acid and ribonucleic acid contents. Each index was in a regression equation best to describe the pattern of mammary growth. These included linear, quadratic, cubic, and exponential model Y = AebX in which Y was the index of mammary growth and X was the day of pregnancy. Total deoxyribonucleic acid was the best index of mammary growth with a correlation of .95 in the exponential model. The predictive equation for total deoxyribonucleic acid in milligram was Y = 167e.019X on a daily basis, and the rate of growth on a monthly basis was .57. Mammary growth in goats continued into early lactation, peaking at day 5. Ribonucleic acid doubled on the day after parturition, which reflected the rapid increase in protein synthesis at this time.