Androgen Synthesis Modulation by Prostaglandin E2 Is Differentially Mediated via Adenylate Cyclase and Phospholipase C in the Testis of the Crested Newt, Triturus carnifex: In Vitro Studies

Background: Pituitary adenylate cyclase activating peptide-38 (PACAP-38) has been shown to induce migraine in migraineurs, whereas the related peptide vasoactive intestinal peptide (VIP) does not. In the present study we examine the hypothesis that PACAP-38 and its truncated version PACAP-27 but not VIP cause degranulation of mast cells in peritoneum and in dura mater. Methods: The degranulatory effects of PACAP-38, PACAP-27 and VIP were investigated by measuring the amount of N-acetyl-β-hexosaminidase released from isolated peritoneal mast cells and from dura mater attached to the skull of the rat in vitro. In peritoneal mast cells N-truncated fragments of PACAP-38 (PACAP(6–38), PACAP(16–38) and PACAP(28–38)) were also studied. To investigate transduction pathways involved in mast cell degranulation induced by PACAP-38, PACAP-27 and VIP, the phospholipase C inhibitor U-73122 and the adenylate cyclase inhibitor SQ 22536 were used. Results: The peptides induced degranulation of isolated peritoneal mast cells of the rat with the following order of potency: PACAP-38 = PACAP(6–38) = PACAP(16–38) » PACAP-27 = VIP = PACAP(28–38). In the dura mater we found that 10−5 M PACAP-38 was significantly more potent in inducing mast cell degranulation than the same concentration of PACAP-27 or VIP. Inhibition of intracellular mechanisms demonstrated that PACAP-38-induced degranulation is mediated by the phospholipase C pathway. Selective blockade of the PAC1 receptor did not attenuate degranulation. Conclusion: These findings correlate with clinical studies and support the hypothesis that mast cell degranulation is involved in PACAP-induced migraine. PACAP-38 has a much stronger degranulatory effect on rat peritoneal and dural mast cells than VIP and PACAP-27. The difference in potency between PACAP-38- and PACAP-27/VIP-induced peritoneal mast cell degranulation is probably not related to the PAC1 receptor but is caused by a difference in efficacy on phospholipase C.

Download Full-text

The existence of distinct classes of prostaglandin E2 receptors mediating adenylate cyclase and phospholipase C pathways in osteoblastic clone MC3T3-E1

Prostaglandins Leukotrienes and Essential Fatty Acids ◽

10.1016/0952-3278(92)90053-l ◽

1992 ◽

Vol 46 (1) ◽

pp. 15-20 ◽

Cited By ~ 14

Author(s):

K. Toriyama ◽

I. Morita ◽

S.-i. Murota

Keyword(s):

Adenylate Cyclase ◽

Prostaglandin E2 ◽

Phospholipase C

Download Full-text

Effects of pituitary adenylate-cyclase activating peptide (pacap) on the rat adrenal secretory activity: preliminary in-vitro studies

Life Sciences ◽

10.1016/0024-3205(94)00423-p ◽

1995 ◽

Vol 56 (2) ◽

pp. 135-142 ◽

Cited By ~ 32

Author(s):

P Andreis

Keyword(s):

Adenylate Cyclase ◽

Secretory Activity ◽

In Vitro Studies ◽

Pituitary Adenylate Cyclase

Download Full-text

Differential effects of prostaglandin E2 on contractions of airway smooth muscle

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.3.1397 ◽

1989 ◽

Vol 66 (3) ◽

pp. 1397-1407 ◽

Cited By ~ 3

Author(s):

J. M. Madison ◽

C. A. Jones ◽

R. M. Sankary ◽

J. K. Brown

Keyword(s):

Smooth Muscle ◽

Adenylate Cyclase ◽

Prostaglandin E2 ◽

Cyclase Activity ◽

Adenylate Cyclase Activity ◽

Tracheal Smooth Muscle ◽

Inhibitory Effects ◽

Camp Content

In an in vitro muscle bath, the active tension generated by strips of canine tracheal smooth muscle responding to cumulative additions of either histamine (10(-8) to 10(-3) M) or acetylcholine (10(-9) to 10(-3) M) was measured in the absence and presence of prostaglandin E2 (PGE2) (10(-6) to 10(-5) M). When contractile responses of equal magnitude were compared, the contractions elicited by acetylcholine were resistant to the inhibitory effects of PGE2, relative to comparable contractions elicited by histamine. To assess the role of adenylate cyclase in determining the different responses to histamine and acetylcholine in the presence of PGE2, we assayed adenylate cyclase activity in membranes prepared from canine tracheal smooth muscle and found that acetylcholine, but not histamine, decreased PGE2-stimulated adenylate cyclase activity by 48 +/- 2% (mean +/- SE; n = 5). However, in other experiments, we found that even large pharmacological increases in tissue adenosine 3′,5′-cyclic monophosphate (cAMP) content only partially inhibited muscarinic tone. Also, exogenously applied analogues of cyclic AMP inhibited contractions induced by histamine more effectively than comparable contractions induced by acetylcholine. We concluded that acetylcholine decreased adenylate cyclase activity in membranes prepared from canine tracheal smooth muscle and that this effect may have contributed to, but did not completely account for, the relative resistance of muscarinic contractions to the inhibitory effects of PGE2.

Download Full-text

Presence of pituitary adenylate cyclase-activating polypeptide 38-immuno-like material in the brain and ovary of the female crested newt, Triturus carnifex: its involvement in the ovarian synthesis of prostaglandins and steroids

Journal of Endocrinology ◽

10.1677/joe.0.1520141 ◽

1997 ◽

Vol 152 (1) ◽

pp. 141-146 ◽

Cited By ~ 19

Author(s):

A Gobbetti ◽

M Zerani ◽

A Miano ◽

M Bramucci ◽

O Murri ◽

...

Keyword(s):

Adenylate Cyclase ◽

Phospholipase C ◽

Prostaglandin Synthesis ◽

Prostaglandin E ◽

Ovarian Steroidogenesis ◽

Pituitary Adenylate Cyclase ◽

Crested Newt ◽

The Brain

Abstract The presence of pituitary adenylate cyclase-activating peptide (PACAP) 38-immuno-like material (PACAP 38-IL) in the brain and ovary of the crested newt, Triturus carnifex, and its action on ovarian steroidogenesis and prostaglandin synthesis were evaluated. The HPLC brain and ovary extract peaks that eluted like PACAP 38 were considered PACAP 38-like material. The concentrations of PACAP 38-IL in the HPLC extracts were measured by RIA. T. carnifex ovary was incubated with PACAP 38, brain and ovary PACAP 38-IL, and inhibitors of cyclooxygenase (COX), adenylate cyclase (AC) and phospholipase C (PLC) for 30 and 60 min. PACAP 38, and brain and ovary PACAP 38-IL increased prostaglandin E2 (PGE2) (30 and 60 min), and progesterone and corticosterone (60 min), but decreased oestradiol-17β (60 min). COX and PLC inhibitors counteracted the increases in PGE2, progesterone and corticosterone and the decrease in oestradiol-17β, and the AC inhibitor also counteracted them except for PGE2. These results suggest that PACAP 38-IL, present in T. carnifex brain and ovary, acts on PLC, inducing the increase of PGE2 which, in turn, acting on AC, induces increases in progesterone and corticosterone and a decrease in oestradiol-17β. Journal of Endocrinology (1997) 152, 141–146

Download Full-text