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Biomedical subjects

A Cowan

Publications and source records attributed to A Cowan.

172 records · Page 10Linked to original sources
PubMedDate not supplied

Estimation of the dissociation constant of naloxone in the naive and morphine-tolerant guinea-pig isolated ileum: analysis by the constrained Schild plot.

The pA2 values for naloxone-morphine were determined using ilea taken from naive and morphine-tolerant guinea-pigs. This constant decreased from 8.56 (+/- 0.22) in the naive to 7.95 (+/- 0.12) in tolerant tissues. The values of the pA2's were based on Schild plots using conventional regression techniques; this regression resulted in values of -log KB of 8.79 (+/- 1.5) and 8.18 (+/- 1.2) in naive and morphine-tolerant ilea, respectively. While pA2 differed, the difference in -log KB was not statistically significant. Since these two values are theoretically equivalent, the above finding appears paradoxical. Constraining the slope of the Schild plot to the theoretically required -1 resolved this discrepancy by reducing the error inherent in the calculation of -log KB determined by conventional regression.

Animals↗
PubMedDate not supplied

In vivo and in vitro studies with agents that cause quasi-morphine withdrawal syndromes.

Compounds that elicit a "quasi-morphine withdrawal syndrome" (QMWS) after acute administration to rats constitute a new class of behavior-modifying agent. In studying the pharmacological bases of quasi-opiate withdrawal syndromes, we found that the dihydrocodeinone, RX 336-M, a standard QMWS-inducing agent, caused a naloxone-insensitive increase in twitch tension on the field-stimulated rat was deferens preparation. In contrast, IBMX (3-isobutyl-1-methylxanthine), the historical inducer of quasi-abstinence in rats, gave a naloxone-insensitive decrease in twitch tension. Tolerance developed to the "wet-dog" shakes elicited by twice-daily s.c. injections of RX 336-M or IBMX in rats for 5 or 15 days, respectively. The parallel development of tolerance to the in vitro effects of these compounds could not be demonstrated.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

Studies on bombesin-induced grooming in rats.

The gross behavior induced by centrally administered bombesin in rats was compared to that elicited by ACTH-(1-24) and the somatostatin analog, des AA1,2,4,5,12,13[D-Trp8]-somatostatin (ODT8-SS). Bombesin (0.001-1 microgram, ICV) caused dose-related excessive scratching which was qualitatively different from that associated with the other two groom-inducing agents. Bombesin-induced grooming was not markedly affected by behaviorally nondepressant doses of haloperidol, morphine, naloxone or neurotensin. Bombesin was active in genetically hypotrichotic (essentially furless) rats; and, again in such animals, even after numbing the area caudal to the shoulders with lidocaine. Tolerance and cross-tolerance studies with bombesin and ODT8-SS indicated that they produce scratching through different mechanisms. Bombesin caused scratching when injected directly into the periaqueductal gray, but not when administered intravenously. Neither hypophysectomy nor adrenalectomy markedly affected bombesin-induced grooming. This behavior appears to be initiated in the central nervous system and is produced independently of the pituitary-adrenal axis.

Animals↗
PubMedDate not supplied

Pituitary opioid involvement in ECS-postictal electrogenesis and behavioral depression in rats.

The role of pituitary opioids in electroconvulsive shock (ECS)-induced postictal electrogenesis and behavioral depression was investigated in sham-hypophysectomized and hypophysectomized rats. These animals were divided into two subgroups and injected SC with either saline or naloxone (3 mg/kg) 10 min prior to transauricular ECS. Sham-hypophysectomized rats given saline responded to a single ECS with a 65 +/- 18% (s.e.) increase in postictal electrogenesis and a behavioral depression lasting 3840 +/- 530 sec. Naloxone significantly antagonized both the postictal increase in EEG voltage output and behavioral depression. Hypophysectomy by itself was without effect on EEG patterns and only partially attenuated the ECS-induced electrogenesis and postictal depression (31.9 +/- 9% and 2360 +/- 511 sec, respectively). However, in hypophysectomized rats, naloxone did not further antagonize these effects of ECS. Thus, it appears that pituitary opioids may, at least in part, mediate postictal electrogenesis and behavioral depression. Alternatively, since hypophysectomy only partially attenuates these phenomena, central or nonpituitary opioid peptide systems may be involved. In view of the observed decrease in responsiveness to naloxone in hypophysectomized rats, nonopioid systems cannot be ruled out as contributors to the opioid-like effects of ECS in these animals.

Animals↗
PubMedDate not supplied

Two bombesin analogues discriminate between neuromedin B- and bombesin-induced calcium flux in a lung cancer cell line.

We examined the profile of two bombesin (BN) antagonists, (CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3] (ICI 216140) and [D-Phe6,des-Met14]BN(6-14)ethylamide (DPDM-BN EA), against neuromedin B-induced Ca2+ mobilization in the small cell lung cancer (SCLC) line NCI-H345. Neuromedin B (NMB), a BN-like peptide sharing sequence homology with ranatensin, elicited a concentration-dependent Ca2+ release (in part) from intracellular stores. Sequential addition of NMB attenuated Ca2+ mobilization. Desensitization occurred between BN and NMB; depletion of intracellular Ca2+ is a likely mechanism because thapsigargin stimulated Ca2+ release after a maximally desensitizing dose of NMB. ICI 216140 and DPDM-BN EA competitively inhibited BN-induced Ca2+ transients. In contrast, these compounds antagonized NMB-stimulated Ca2+ transients in a noncompetitive manner. The pharmacological profiles obtained support receptor heterogeneity for BN-like peptides on this SCLC line, underscoring the need for thorough examination of dose-response relationships when investigating effects of BN analogues on intact cells.

Amino Acid Sequence↗
PubMedDate not supplied

5 A Day for better health--nine community research projects to increase fruit and vegetable consumption.

One of the national objectives in "Healthy People 2000" is for members of the public to increase their consumption of fruits and vegetables to five or more servings daily. The National Cancer Institute (NCI) began a nationwide campaign to achieve this objective in 1991. As part of this campaign, the NCI funded nine research studies in 1993. These projects are implementing and evaluating community-based programs designed to increase fruit and vegetable consumption among different segments of the population in Alabama, Arizona, Georgia, Louisiana, Maryland, Massachusetts, Minnesota, North Carolina, and Washington. The settings for these projects include the Special Supplement Food Program for Women, Infants, and Children (WIC Programs), churches, worksites, and schools. The projects are led by multidisciplinary teams and entail extensive collaboration among academic, governmental, private sector, and voluntary agencies within each State. The projects represent a model public health paradigm for conducting this type of research.

Diet↗