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H E Hopkinson

Publications and source records attributed to H E Hopkinson.

4 recordsLinked to original sources
PubMed2000

Non-competitive antagonism of beta(2)-agonist-mediated cyclic AMP accumulation by ICI 118551 in BC3H1 cells endogenously expressing constitutively active beta(2)-adrenoceptors.

Constitutive activity of the beta(2)-adrenoceptor, which is sensitive to inhibition by an inverse agonist such as ICI 118551, has been readily demonstrated in recombinant systems expressing constitutively-active mutant receptors or over-expressing the wild-type beta(2)-adrenoceptor. Here we demonstrate the presence of constitutive beta(2)-adrenoceptor activity in BC3H1 cells which endogenously express this receptor. In BC3H1 cells, only ICI 118551 behaved as an inverse agonist at beta(2)-adrenoceptors, while propranolol, ICI 118551, atenolol and, to a lesser extent, alprenolol exhibited inverse agonism in CHO-beta(2)4 cells transfected with cDNA for the human beta(2)-adrenoceptor (310 fmol. mg protein(-1)). The level of expression of beta2-adrenoceptors in BC3H1 cells was not high (78 fmol.mg protein-1) and the efficiency of receptor - effector coupling in this cell line was much lower than in the recombinant CHO-beta(2)4 cells (as judged by the partial agonist nature of both salbutamol and clenbuterol). ICI 118551 (log K(D)-9.73+/-0.07) and propranolol (log K(D)-9.25+/-0.12) both behaved as conventional competitive antagonists of isoprenaline-stimulated cyclic AMP accumulation in high expressing CHO-beta(2)4 cells. In contrast, ICI 118551 appeared to act as a non-competitive antagonist in BC3H1 cells and in low expressing CHO-beta(2)6 cells (50 fmol.mg protein(-1)). This non-competitive effect of ICI 118551 in BC3H1 cells was also observed when either salbutamol was used as agonist, or the incubation period with isoprenaline was extended to 30 min. The possibility that these effects of ICI 118551 are due to an interaction with different affinity states (R, R* and R') of the receptor is discussed.

Adrenergic beta-2 Receptor Agonists↗
PubMed1992

The nature of breast dense core granules: chromogranin reactivity.

Ultrastructural immunoreactivity for chromogranin with the LK2H10 antibody was examined in nine cases of breast carcinoma and one example of normal resting breast. These tissues were selected for study on the basis of argyrophilia or LK2H10 immunostaining by light microscopy. In two cases, positive reactivity with the chromogranin antibody was seen in breast neuroendocrine-like dense core granules. In a further six cases chromogranin reactivity was not seen in similar granules that showed the neuroendocrine properties of ultrastructural argyrophilia and uranaffinity. Inability to exhibit the full complement of neuroendocrine characteristics in breast carcinomas contrasts with the facility to demonstrate them in tissues of usual neuroendocrine differentiation. Furthermore, in two mucoid carcinomas and one example of normal resting breast ultrastructural cytoplasmic LK2H10 reactivity was evident, which was not localized to dense core granules, although these were present in two of the cases. Our findings demonstrate the heterogeneity of breast dense core granules and discourage acceptance of such characteristics as evidence of histogenesis of these carcinomas from a neuroendocrine cell type in breast tissue.

Adenocarcinoma, Mucinous↗
PubMed1987

The nature of breast dense core granules: uranaffin reactivity.

In this study breast tissue that contained ultrastructural dense core granules has been examined from 24 patients. The possible neuroendocrine characteristics of the granules were studied using the uranaffin reaction and an ultrastructural argyrophil stain. The tissue included 15 breast carcinomas and nine benign samples. Two types of breast dense core granules can be distinguished on the basis of intracellular distribution patterns and histochemical reactivity. Type I dense core granules are the most common and they were found subluminally distributed in non-pathological tissues and benign lesions as well as carcinomas. They were uranaffin-negative and are unlikely to be of endocrine nature. Type II dense core granules were found only in four carcinomas, where they occurred abundantly throughout the cytoplasm. These granules were uranaffin-positive and argyrophilic and thus exhibited characteristics consistent with neuroendocrine structure.

Breast↗