Biomedical subjects

R G Pendleton

Publications and source records attributed to R G Pendleton.

At least 73 records · Page 4Linked to original sources

PubMed1976

The long term effects of an inhibitor of phenylethanolamine N-methyltransferase upon adrenal epinephrine biosynthesis.

Chronic administration of SK&F 64139, an inhibitor of phenylethanolamine N-methyltransferase (PNMT), initially resulted in a lowered adrenal epinephrine content in both the rat and squirrel monkey adrenal gland. With continued dosing, however, these levels returned toward control. The latter changes were accompanied by increased adrenal levels of norepinephrine and PNMT, but not by decreased plasma drug levels. These results suggest that long-term pharmacological PNMT inhibition may evoke compensatory mechanisms to maintain adrenal epinephrine biosynthesis under basal laboratory conditions.

Adrenal Medulla↗

PubMed1976

Studies concerning dopamine diuresis in the rat.

Dopamine is both diuretic and saluretic in the conscious rat. The diuretic effect does not appear to be beta-receptor mediated, but rather may be the result of a combination of alpha- and dopaminergic receptor stimulation. Conclusive proof for the existence of the latter, however, must await the discovery of a more selective peripheral dopamine-receptor stimulant than is dopamine per se.

Animals↗

PubMed1976

Studies on adrenal phenylethanolamine N- methyltransferase (PNMT) with S K & F 64139, a selective inhibitor.

SK&F 64139 is a potent, reversible inhibitor of phenylethanolamine N-methyltransferase; its IC50 concentration in our standard assay system was 1 X 10(-7) M. Kinetically, the compound is a competitive inhibitor with respect to norepinephrine but is uncompetitive when S-adenosylmethionine is the variable substrate. In contrast to a previously reported compound (SK&F 7698), the drug is only a weak alpha receptor antagonist (KB = 6 X 10(-6) M). In both the rat and squirrel monkey, SK&F 64139 produced dose-dependent decreases in the adrenal epinephrine content coupled with stoichiometrically equivalent increases in the norepinephrine pool(s). Further evidence for in vivo phenylethanolamine N-methyltransferase inhibitory activity was that the drug markedly inhibited the conversion of a tracer dose of 3H-norepinephrine to 3H-epinephrine in the rat adrenal gland after unit oral doses as low as 5 mg/kg.

Adrenal Glands↗

PubMed1976

Studies on the action and interaction of dopamine and prostaglandin A1 in the renal vasculature.

Dopamine (3 mug/kg/min) and prostaglandin A1 (0.2 mug/kg/min) were found to dilate the renal vasculature and increase total kidney blood flow in be anesthetized dog. These effects of dopamine, but not of prostaglandin A1, were completely antagonized by bulbocapnine, a selective dopamine receptor inhibitor, at a dose (3 mg/kg) which did not itself significantly alter cardiovascular hemodynamics. Conversely, indomethacin, an inhibitor of prostaglandin synthetase in the dog at 2 mg/kg, did not reduce the dopamin renal vascular response. These results suggest that dopamine and PGA1 decrease renal vascular resistance in the dog via distinct pharmacological mechanisms.

Animals↗

PubMed1975

Effect of bulbocapnine as a peripheral dopamine receptor antagonists in the anesthetized cat.

We have found bulbocapnine to be an effective, apparently competitive inhibitor of dopamine depressor responses in the anesthetized, phenoxybenzamine-treated cat. The duration of action of the compound as a dopaminergic antagonist exceeded 3 hrs after an intravenous dose of 8 mg/kg. In the same preparation, however bulbocapnine did not at all inhibit the depressor responses to acetylcholine, histamine and isoproterenol, indicating a selectivity of action. Although administration of a high dose of propranolol (2 mg/kg, i.v.) did not alter the response of the alpha-receptor blocked cat to dopamine, the subsequent infusion of bulbocapnine remained effective. These results suggest that dopamine is acting as a blood pressure depressor agent via a unique receptor mechanism.

Anesthesia↗

PubMed1975

The cardiovascular actions of dopamine and the effects of central and peripheral catecholaminergic receptor blocking drugs.

The cardiovascular effects of dopamine (DA) were studied in anesthetized dogs with special attention to the susceptibility of these effects to inhibition by catecholaminergic receptor blocking drugs. Dopamine given by rapid i.v. injection at 1 and 3 mug/kg produced depressor responses whereas doses from 9 to 81 mug/kg produced pressor resposes and increases in cardiac contractile force. Propranolol inhibited the increases in cardiac contractility whereas phenoxybenzamine potentiated the depressor effect of low doses of DA and reversed the pressor effect of high doses. Bulbocapnine blocked the depressor effect of DA in both phenoxybenzamine and propranolol-treated dogs. Pimozide, however, had no effect on the depressor response to DA. In hemodynamic studies, DA reduced blood pressure, total peripheral resistance and renal vascular resistance. Cardiac output and renal blood flow were increased. Bulbocapnine, but not pimozide, abolished the effects of DA on blood pressure, vascular resistance and renal blood flow. In conscious dogs, pimozide abolished apomorphine-induced emesis (an effect mediated by DA receptors in the central nervous system) whereas bulbocapnine had no effect. Therefore, the peripheral vascular and central dopamine receptors may be pharmacologically distinct.

Animals↗

PubMed1975